Startseite Naturwissenschaften Synthesis and antiproliferative evaluation of some 1,4-naphthoquinone derivatives against human cervical cancer cells
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Synthesis and antiproliferative evaluation of some 1,4-naphthoquinone derivatives against human cervical cancer cells

  • Aysecik Kacmaz , Nahide Gulsah Deniz , Serdar Goksin Aydinli , Cigdem Sayil EMAIL logo , Evren Onay-Ucar , Elif Mertoglu und Nazli Arda
Veröffentlicht/Copyright: 24. April 2019
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Open Chemistry
Aus der Zeitschrift Open Chemistry Band 17 Heft 1

Abstract

In the course of biological properties of quinone derivatives, the N(H)-, S- and S,S-substituted-1,4-naphthoquinones were synthesized by reactions of 2,3-dichloro-1,4-naphthoquinone with different amines (2-morpholinoaniline, tert-butyl 4-aminobenzoate, 4-tert-butylbenzylamine, N-(3-aminopropyl)-2-pipecoline, 2-amino-5,6-dimethylbenzothiazole, N,N'-diphenyl-p-phenylenediamine) and thiolat (sodium 2-methyl-2-propanethiolate). All new products were characterized by MS-ESI, UV-Vis, FT-IR, 1H NMR, 13C NMR. The antiproliferative activities of these compounds on human cervical cancer (HeLa) cells were evaluated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. Although all derivatives inhibited cell growth, the most active compound was 2-(tert-butylthio)-3-chloronaphthalene-1,4-dione 5 (IC50=10.16 μM) against the HeLa cells.

Keywords: Quinones; Amines; Thiols; Antiproliferative activity; HeLa cell

1 Introduction

Naturally occurring and synthetic naphthoquinones have found wide uses in pharmacological fields with their antiseptic [1], antifungal, antibacterial [2], anti-inflammatory [3,4], cytotoxic [5-7], anti-tumor [3,8, 9, 10], molluscicidal [11], anticancer [12-14], antimicrobial [3,15], antimalarial [16,17], antithrombotic [3], etc. activities. Thus, many naphthoquinone derivatives have been synthesized [7,8,18, 19, 20, 21] and some of them have been patented [4,22]. However, there is still a continuous effort to find functionalized naphthoquinones and related compounds. Also, the incorporation of amino, thio, halo or alkyl/aryl group into quinones could be used to improve their antifungal, antibacterial, cytotoxic etc. activities [7, 23, 24, 25].

Recently, quinones have gained importance for their uses in chemotherapy (anticancer drugs), such as mitomycin C, doxorubicin, daunorubicin, streptonigrin, idarubicin, mitoxantrone, epirubicin etc [12,21, 26, 27, 28, 29]. Generally, the anticancer properties of the compounds having the quinone structure seem to be due to the induction of oxidative stress [7,30]. Among quinones, 1,4-naphthoquinones such as alkannin, shikonin, 2-hydroxynaphthoquinone, 1,2-pyranonaphthoquinone derivatives have been offered as potential drug candidates for cancer treatment [12,31,32].

Several studies highlight the antiproliferative/anticancer activity of 1,4-naphthoquinone compounds on prostate, breast, lung, colon, brain and pancreas cancer cells [12, 14, 29, 32, 33, 34]. Forexample, some 1,4-napthoquinone derivatives showed improved antiproliferative activity in comparison to the lead molecule in prostate (DU-145), breast (MDA-MB-231) and colon (HT-29) cancer cell lines [13]. Also, the literature mentions that some compounds similar to those synthesized in this study, for example 2-chloro-3-(N-alkylamino)-1,4-napthoquinone derivatives exhibit antiproliferative activities on colon (COLO205), brain (U87MG) and pancreas (MIAPaCa2) cancer cells [29]. Besides, the antiproliferative activity of 2-(4-morpholinophenylamino)-3- chloronaphthalene-1,4-dione has been found to be comparable to that of the proteasome inhibitor PI-083 [20]. This compound is similar to synthesized compound 3a in this study.

It has been previously known that some mono-, bis-, tris- and tetrakis-(thio/amino)-quinone derivatives synthesized in our laboratory [35-41] have antifungal, antibacterial, antioxidant and cytotoxic/anticancer activities [38,39]. The N-substituted napthoquinone compound showed the powerful cytotoxic activity at a concentration of 20 μM against A549 (lung), MCF-7 (breast), DU145 (prostate), and HT-29 (colon) cancer cell lines [39]. Thus, due to the promising anticancer activities of quinone compounds, we report in this work the synthesis, characterization and antiproliferative activity of N(H)-, S- and S, S-substituted-1,4-naphthoquinones.

2 Experimental

2.1 Chemistry

Melting points were determined using Buchi B-540 equipment. Infrared spectra (IR) were recorded on Thermo Scientific Nicolet 6700 instrument. Mass spectra (MS) were taken from Thermo Finnigan LCQ Advantage MAX, operated in positive and negative ion mode (+ESI and - ESI). 1H NMR, 13C NMR spectrums were obtained using a Varian Unity Inova (500 MHz) spectrometer by using TMS as the internal standard and deuterated chloroform as solvent. UV-Vis spectra were obtained by using a Lambda 35 UV/Vis Spectrometer (Perkin Elmer) in CHCl3. Column chromatography on silica was performed (Merck Kieselgel 60, 70-230 mesh). Unless otherwise stated reagents were purchased from Sigma Aldrich, USA.

2.2 Experimental Design of the Compounds

2-(2-Morpholinophenylamino)-3-chloronaphthalene-1,4-dione (3a). A solution of 1.2 g 1 (5.28 mmol) and 0.94 g 2-morpholinoaniline 2a (5.28 mmol) in 30 mL ethanol was heated under a reflux condenser without base. The reaction medium was monitored by thin layer chromatography and the mixture was then diluted with water and extracted with chloroform. The CHCl3 extract was dried with anhydrous Na2SO4 and concentrated in under pressure to give a crude product, which was chromatographed with silica gel column to give 0.78 g (40%) 3a. Rf (CH2Cl2): 0.23; Black solid; mp 175-176°C; IR (KBr, cm-1): 3300, 2960, 2852, 1674, 1647, 1604, 1569; UV λmax (CHCl3 nm (log ε): 241 (3.63), 284 (3.93), 521 (3.17); 1H NMR (500 MHz, CDCl3): δ 8.13 (H, dd, CHnaphtJ = 7.8 Hz, 1.5 Hz), 8.02 (H, dd, CHnapht, J = 7.6 Hz, 1.2 Hz), 7.87 (H, s, NH), 7.70 (H, td, CHnapht, J = 7.6 Hz, 1.3 Hz), 7.61 (H, td, CHnapht, J = 7.6 Hz, 1.4 Hz), 7.09 (H, td, CHaromJ = 7.7 Hz, 1.6 Hz), 7.04-6.98 (2H, m, CHarom), 6.85 (H, dd, CHaromJ= 7.8 Hz, 1.5 Hz), 3.71 (4H, t, 2 O-CH2-, J = 4.4 Hz), 2.89 (4H, t, 2N-CH2-, J = 4.4 Hz); 13C NMR (125 MHz, CDCl3): δ 179.5, 176.0 (C=O), 143.6,140.7,133.9,131.9,131.7,130.8,129.2,126.2,126.1,125.9, 124.4, 122.8, 118.3, 114.2 (Cnapht, CHnapht, CHarom, Carom) 66.3, 66.2 (-H2C-O-), 50.6, 50.7 (-N-H2C-); MS (+ESI): m/z = 369.0 [M+H]+, MS/MS (+ESI) : m/z = 333.1 [M-Cl]+.

Ter t-butyl-4-(2-chloro-1,4-dihydro-1,4-dioxonaphthalen-3-ylamino)benzoate (3b). A solution of 1.5 g 1 (6.60 mmol) and 1.28 g tert-butyl 4-aminobenzoate 2b (6.60 mmol) in 30 mL ethanol was heated under reflux condition without base. The reaction medium was monitored by thin layer chromatography and the mixture was then diluted with water and extracted with chloroform. The CHCl3 extract was dried with anhydrous Na2SO4 and concentrated in under pressure to give a crude product, which was chromatographed with silica gel column to give 1.42 g (56%) 3b. Rf (CHCl3): 0.3; Red solid; mp 104-105°C; IR (KBr, cm-1): 3185, 2977, 2931, 1705, 1676, 1651, 1595, 1570; UV λmax (CHCl3) nm (log ε): 240 (4.37), 290 (4.72), 472 (3.83); 1H NMR (500 MHz, CDCl3): δ 8.12 (1H, dd, CHnapht, J = 7.8 Hz, 1.0 Hz), 8.05 (1H, dd, CHnapht, J = 7.6 Hz, 1.2 Hz), 7.64 (1H, td, CHnapht, J = 7.6 Hz, 1.3 Hz), 7.71 (1H, td, CHnapht, J = 7.5 Hz, 1.5 Hz), 7.63 (H, s, NH), 7.90 (2H, dd, CHarom, J = 8.3 Hz, 2.1 Hz), 6.97 (2H, d, CHarom, J = 8.8 Hz), 1.53 (9H, 3CH3); 13C NMR (125 MHz, CDCl3): δ 179.4, 176.4 (C=Onapht), 164.1 (-O-C=O-), 140.1, 140.0, 134.1, 132.2, 131.4, 128.9, 128.9, 128.8, 127.5, 126.2, 126.1, 121.7, 121.6, 116.2 (CHnapht, Cnapht, Carom, CHarom), 80.1 (Ctert), 27.2, 27.2 (Me); MS (+ESI): m/z = 384.0 [M+H]+, MS (-ESI): m/z = 382.1 [M-H]-, MS/MS (-ESI): m/z = 326.2 [M-(CCH3)3]-.

2 - (4 -Tert- butylbenzylamino) - 3 - chloronaphthalene-1,4-dione (3c). A solution of 1.0 g 1 (4.4 mmol) and 0.72 g 4-tert-butylbenzylamine 2c (4.4 mmol) in ethanol at room temperature was stirred without base. The reaction medium was monitored by thin layer chromatography and the mixture was then diluted with water and extracted with chloroform. The CHCl3 extract was dried with anhydrous Na2SO4 and concentrated in under pressure to give a crude product, which was chromatographed with silica gel column to give 0.74 g (47%) 3c. Rf (CHCl3): 0.6; Red solid; mp 101-102°C; IR (KBr, cm1): 3340, 2963, 2904, 2868, 1679, 1646, 1602, 1573; UV Amax (CHCl3) nm (log ε): 241 (3.12), 278 (4.34), 455 (2.38); m NMR (500 MHz, CDCl3): S 8.09 (1H, dd, CHnapht, J = 7.8 Hz, 1.5 Hz), 7.97 (1H, dd, CHnapht, J = 7.8 Hz, 1.5 Hz), 7.66 (1H, td, CHnapht, J = 7.4 Hz, 1.1 Hz), 7.56 (1H, td, CHnapht, J = 7.4 Hz,

1.3 Hz), 7.34 (2H, dd, 2CHarom, J = 6.4 Hz, 2.0 Hz), 7.20 (2H, d, 2CHarom, J = 8.3Hz), 6.11 (s, H, NH), 4.95 (d, 2H, CH2benzyl, J = 5.9 Hz), 1.26 (s, 9H, 3CH3); 13C NMR (125 MHz, CDCl3): d 179.5, 175.9 (C=O), 150.2, 143.1, 133.9, 133.8, 131.7, 131.5, 128.9, 128.7, 126.5, 126.0, 125.9, 125.8, 125.6, 125.0 (CHnapht, Cnapht, CHarom, Carom), 47.8 (CH2benzyl), 33.6 (Ctert), 30.3 (3CH3); MS (+ESI): m/z = 354.1 [M+H]+.

2-(3-(2-Methylpiperidin-1-yl)propylamino)-3-chloronaphthalene-1,4-dione (3d). A solution of 1.0 g 1 (4.4 mmol) and 0.63g N-(3-aminopropyl)-2-pipecoline 2d (4.4 mmol) in ethanol at room temperature was stirred without base. The reaction medium was monitored by thin layer chromatography and the mixture was then diluted with water and extracted with chloroform. The CHCl3 extract was dried with anhydrous Na2SO4 and concentrated in under pressure to give a crude product, which was chromatographed with silica gel column to give 0.62 g (40%) 3d. Rf(EtOH): 0.35; Red viscous oil; IR (KBr, cm-1): 3343, 2933, 2856, 2794, 1678, 1634, 1601, 1570; UV λmax (CHCl3) nm (log ε): 241 (4.19), 276 (4.38), 467 (3.53); 1H NMR (500 MHz, CDCl3): d 8.07 (dd, H, CHnapht, J = 7.8 Hz, 1.0 Hz), 7.96 (dd, H, CHnapht, J = 7.8 Hz, 1.0 Hz), 7.63 (td, H, CHnapht, J = 7.6 Hz, 1.1 Hz), 7.53 (td, H, CHnapht, J = 7.6 Hz, 1.3 Hz), 7.34-7.48 (sb, H, NH), 3.80-4.10 (m, 2H, CH2), 2.80-3.0 (m, broad, 2H, CH2), 1.0-2.5 (m,14H, CH2ring, CH2, CH3); 13C NMR (125 MHz, CDCl3): d 179.7, 178.0 (C=O), 143.9, 133.7, 131.8, 131.2, 129.1, 125.7, 125.7 (Cnapht, C-Hnapht), 55.9, 51.1, 43.8, 32.5, 28.7, 25.2, 24.0, 22.3; 17.3 (CH3); MS (+ESI): m/z = 346.9 [M+H]+.

2-(5,6-Dimethylbenzo[d]thiazol-2-ylamino)-3-chloronaphthalene-1,4-dione (3e). A solution of 2.0 g 1 (8.8 mmol) and 2-amino 5,6-dimethylbenzothiazole 1.56 g 2e (8.8 mmol) in 30 mL ethanol was stirred at reflux temperature without base. The reaction medium was monitored by thin layer chromatography and the mixture was then diluted with water and extracted with chloroform. The CHCl3 extract was dried with anhydrous Na2SO4 and concentrated in under pressure to give a crude product, which was chromatographed with silica gel column to give 0.66 g (20%) 3e. Rf(CHCl3): 0.1; Dark orange solid; mp 182-183°C; IR (KBr, cm-1): 3106, 3020, 2962, 2922, 2848, 1679, 1669, 1603, 1576, 1457; UV λmax (CHCl3) nm (log ε): 241 (4.63), 286 (4.73), 467 (3.84); 1H NMR (500 MHz, CDCl3): d 8.14 (H, dd, CHnapht, J = 7.3 Hz, 1.5 Hz), 8.07 (H, dd, CHnapht, J = 7.1 Hz, 1.2 Hz), 7.73 (H, td, CHnapht, J = 7.6 Hz, 1.5 Hz), 7.67 (H, td, CHnapht, J = 7.6 Hz, 1.3 Hz), 7.51 (s, H, CHarom), 7.42 (s, H, CHarom), 2.29 (s, 6H, 2CH3); 13C NMR (125 MHz, CDCl3): d 178.5, 176.6 (C=O), 157.0, 146.8, 140.8, 134.8, 133.9, 133.1, 132.7, 131.0, 129.1, 126.3, 126.1, 123.0, 120.8, 120.4, 19.1 (CH3), 19.0 (CH3); MS (+ESI): m/z = 369.2 [M+H]+, MS2 (+ESI): m/z = 333.4 [M-Cl]+.

2-(N-phenyl-N-(4-(phenylamino)phenyl)amino)-3-chloronaphthalene-1,4-dione (3f). A solution of 2.0 g 1 (8.8 mmol) and 2.29 g N,N′-diphenyl-p-phenylenediamine 2f (8.8 mmol) in 30 mL DMF was stirred at about 120°C. The reaction medium was monitored by thin layer chromatography and the mixture was then diluted with water and extracted with chloroform. The CHCl3 extract was dried with anhydrous Na2SO4 and concentrated in under pressure to give a crude product, which was chromatographed with silica gel column to give 0.79 g (20%) 3f. Rf (CH2Cl2): 0.7; IR (KBr, cm-1): 3320, 3028, 2955, 2918, 2850, 1673, 1595, 1570, 1513, 1496; UV λmax (CHCl3) nm (log ε): 242 (4.78), 277 (4.71), 490 (3.98); 1H NMR (500 MHz, CDCl3): d 8.13 (H, dd, CHnapht, J = 7.6 Hz, 1.2 Hz), 8.06 (H, dd, CHnapht, J = 7.6 Hz, 1.2 Hz), 8.02 (s, H, NH), 7.70 (H, td, CHnapht, J = 7.7 Hz, 1.5 Hz), 7.62 (H, td, CHnapht, J = 7.5 Hz, 1.5 Hz), 7.29 (t, 4H, CHarom, J = 7.8 Hz), 7.10-7.18 (m, 6H, CHarom), 7.02 (d, 4H, CHarom, J = 6.8 Hz); 13C NMR (125 MHz, CDCl3): d 179.6, 176.5 (C=O), 140.6, 136.5, 134.0, 132.0, 131.6, 128.9, 128.5, 128.4, 127.4, 126.2, 126.0, 124.7, 123.3, 116.8, 114.0.

2-(Tert-butylthio)-3-chloronaphthalene-1,4-dione (5) and 2,3-bis(tert- butylthio)naphthalene-1,4-dione (6). A solution of 0.5 g 1 (2.2 mmol) and 0.24 g sodium 2-methyl-2-propanethiolate 4 (2.2 mmol) in CH2Cl2 at room temperature was stirred without base. The reaction medium was monitored by thin layer chromatography and the mixture was then diluted with water and extracted with chloroform. The CHCl3 extract was dried with anhydrous Na2SO4 and concentrated in under pressure to give a crude product, which was chromatographed with silica gel column to give the pure products 5 and 6:

2-(Tert-butylthio)-3-chloronaphthalene-1,4-dione (5). Yield: 0.09 g (15%); Rf (CHCl3): 0.6; Orange solid; mp 131-132°C; IR (KBr, cm-1): 1681, 1663; UV λmax (CHCl3) nm (log ε): 250 (4.26), 282 (4.32), 340 (3.65), 444 (3.20); 1H NMR (500 MHz, CDCl3): d 8.1 (q, 2H, CHnapht, J = 5.4 Hz), 7.70 (p, 2H, CHnapht, J = 4.4 Hz), 1.40 (s, 9H, 3CH3); 13C NMR (125 MHz, CDCl3): d 179.2, 175.7 (C=O), 150.8 (C-S), 145.5, 133.4, 133.0, 131.2, 130.2, 126.8, 126.4 (Cnapht and C-Hnapht), 52.0 (Ctert), 31.4 (s, 9H, 3CH3); MS (+ESI): m/z = 280.1 [M]+.

2,3-Bis(tert-butylthio)naphthalene-1,4-dione (6). Known compound [35,42]. mp 103-105°C; (103-105°C [35, 423542]). MS (+ESI): m/z [M+H]+ = 334.5 (m/z [M+] = 334.7 [35]).

2.3 Cell Culture and Antiproliferative Activity Assay

An antibiotic-antimycotic mixture [penicillin (100 U/mL), streptomycin (100 μg/mL), and amphotericin B (0.25 μg/

mL)] was purchased from Invitrogen, USA. Other reagents were obtained from Sigma Aldrich, USA.

All processes involving cell cultures were carried out in a biological safety cabinet (Class II laminar flow, Bilser), and cells were grown in a CO2 incubator (Heraeus D-6450). An inverted microscope (Olympus CK2) was used for cell counting when required.

HeLa cells (105 cells/mL) were maintained in Eagle's Minimum Essential Medium (EMEM) supplemented with 10% (v/v) heat-inactivated fetal bovine serum and antibiotic-antimycotic mixture at 37°C in an atmosphere with 5% of carbon dioxide. Synthesized naphthoquinone derivatives and starting compound, 2,3-dichloro-1,4-naphthoquinone 1 were dissolved in EMEM and added to growth medium under aseptic conditions.

The antiproliferative effects of the compunds were examined by using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) test with minor modifications [43]. The assay based on the reduction of MTT to a colored formazan end-product by the action of mitochondrial dehydrogenase in living cells [44]. The cells (1×105 cells/mL) were cultured in 96 well-plates. One day later (after reaching confluence), different concentrations (0.5 μM - 75 μM) of each compound were applied to the cells. At the end of 48 hours of incubation, medium was discarded, and the cells were washed with phosphate buffered saline (PBS). Each well was then loaded with 10 μL MTT stock solution (5 mg/mL) and 90 μL PBS, and the plates were further incubated for 4 hours. Aqueous phase was removed and 200 μL DMSO was added to each well to solubilize the water-insoluble purple formazan crystal. Cell viability was assessed by the measurement of the absorbance at 540 nm in a microplate reader (Eon Microplate Spectrophotometer, Bio-Tek Instruments, Inc. Highland Park, USA). Following formula was used for the calculation:

Cell viability(%)=(Asample/Acontrol)x100

where Asample is the absorbance of the sample detected for the cells treated with test material and Acontrol is the absorbance of control (untreated cells). The IC50 value (dose of the compound inhibiting 50% viability of HeLa cells) was calculated from a plot between cell viability and concentration of the compound. Each test was performed in triplicate.

2.4 Statistical Analysis

Statistical comparisons for the antiproliferative activity test were made using one-way analysis of variance (ANOVA) module of GraphPad Prism 5. Difference in mean values were considered significant when P<0.05.

Ethical approval: The conducted research is not related to either human or animal use.

3 Results and discussion

We initially attempted the synthesis of N(H)-substituted-1,4-naphthoquinones 3a-f by the reaction of 1 with different amines (2-morpholinoaniline 2a, tert-Butyl 4-aminobenzoate 2b, 4-tert-Butylbenzylamine 2c, N-(3-Aminopropyl)-2-pipecoline 2d, 2-Amino-5,6-dimethylbenzothiazole 2e, N,N'-Diphenyl-p-phenylenediamine 2f) in the absence of a base at room / reflux temperature (Scheme 1). This was then followed by 1 reacted with sodium 2-methyl-2-propanethiolate 4 to obtain S- and S,S- substituted compounds (5 and 6, respectively) at room temperature using CH2Cl2 as solvent.

Scheme 1 The synthesis of N(H)-, S- and S,S-substituted-1,4-naphthoquinones.
Scheme 1

The synthesis of N(H)-, S- and S,S-substituted-1,4-naphthoquinones.

1H and 13C NMR spectrums were carried out to obtain characterization of all the synthesized compounds (3a-f, 5 and 6). In the 1H NMR spectrum of 3a-f, the signals for protons Ha and H d of the naphthoquinone ring (Figure 1) in the range 6 7.96-8.14 ppm firstly split into doublets (J3 =7.1-7.8 Hz) because of adjacent proton and then split into doublets of doublets (J4 = 1.0-1.5 Hz). Similarly, doublets of triplets could be detected for Hb and Hc in the range 6 7.53-7.73 ppm with the corresponding coupling constants (J3 = 7.4-7.7 Hz and J4 = 1.1-1.5 Hz), because of ortho (adjacent) and meta position.

Figure 1 Characterization of quinonoid protons Ha-d of the N(H)-substituted 1,4-naphthoquinones (3a-f).
Figure 1

Characterization of quinonoid protons Ha-d of the N(H)-substituted 1,4-naphthoquinones (3a-f).

Analyzing the 1HNMR spectroscopic data of compound 3a it is obvious that the same expected coupling constants of the protons in ring position of O-CH2 and N-CH2- are in agreement with the observed triplet peaks (6 3.71 ppm, J3 = 4.4 Hz and 6 2.89 ppm, J3 = 4.4 Hz, respectively). Its 13C NMR spectrum showed signals for the (-H2C-O-) and (-H2C-N-) carbons at about 6 66 and 50 ppm and two signals for the carbonyl (C=O) carbons (δ 179.5, 176.0 ppm) as expected. Also, the mass spectrum of 3a exhibited at m/z 369.0 ([M+H]+, 100%) as protonated molecular peak, which is agreement with the molecular formula C20H17ClN2O3: 368.81 g.mol-1. Also, this peak selected to fragment in MS/MS (MS2) mode to product m/z = 333.1 [M-Cl]+ fragment ion peak.

The fact that the compound 3b has two types of carbonyl groups can be easily deduced from the peaks at 6 179.4, 176.4 ppm (C=Onapht) and 6 164.1 ppm (C=Oester) in

the 13C NMR spectrum. Also, the chemical shift of 6 80.1 ppm indicates that compound 3b has tert-butyl carbon [(CH3)3C] connected to an oxygen atom and in the negative ion mode, the ESI full mass spectrum of 3b showed the expected deprotonated peak at m/z 382.1 as [M-H]- and the MS/MS fragmentation spectrum of this peak gave one intense peak appearing at m/z 326.2 as [M-(CCH3)3]-. Additionally, in the positive ion mode, compound 3b showed m/z [M+H]+ = 384.0 as protonated molecular ion peak (calculated for 3b: C21H18ClNO4: 383.82 g.mol-1), supporting its proposed identity.

Reaction of 1 with 4-tert-butylbenzylamine 2c in ethanol at room temperature led to a red solid compound 3c. Mass spectrometry data allowed the determination of its protonated molecular ion peak, m/z 354.1 [M+H]+, as expected (calculated for 3c, 353.84 g.mol-1). The doublet at 6 4.95 ppm and the broad singlet at 6 6.11 ppm clearly show the presence of NH-CH2-and NH protons in the compound 3c, respectively and 13C NMR spectrum showed that both the naphthoquinone's carbonyl (6 179.5, 175.9 ppm) and NH-CH2- carbon (47.8 ppm) of 3c, together.

While compound 3d revealed proton signals at 6 1.04.10 ppm (aliphatic protons and cyclic protons) in their expected positions in the 1H NMR spectrum, compound 3e revealed the singlets at 6 7.51 and 7.42 ppm due to the benzothiazole structure in the 1H NMR spectrum. When the reaction of 1 was carried out with an equivalent of the sodium 2-methyl-2-propanethiolate 4 in dichloromethane without any catalyst at room temperature, mono- and bis-thiosubstituted-1,4-naphthoquinone derivatives (5 and 6) were obtained respectively. The mono-thiosubstituted

product 5 showed the signal of naphthoquinone protons at 6 8.1, 7.70 ppm and of methyl protons at 6 1.40 ppm in the 1H NMR spectra and the most characteristic two quinonic carbonyl signals (at δ 179.2 and 175.7 ppm) in the 13C NMR spectra.

For all compounds IR spectra were recorded. For all compounds the characteristic stretching vibrations of quinones (C=O bonds) appeared in the expected range 1655-1680 cm-1 and absorption bands at about between 3100-3350 cm-1 due to NH groups.

The UV-visible absorption spectra of compounds 3a-e were carried out between 190-600 nm in chloroform at room temperature. 3a-e exhibited a maximum absorbance in the 276-290 nm region (π➝π*) and a broad low absorbance in the visible region at 455-521 nm, which could be assigned to n➝π* transitions. In addition, the S-substituted compound 5 showed four prominent bands at 250, 282, 340, and 444 nm.

3.1 Antiproliferative Activity

The antiproliferative effect of each compound on the HeLa cells was investigated by MTT test and final results were given as mean percentages of control ±SD. The IC50 values were predicted from linear regression analyses (Figure 2). The results indicated that all tested compounds have antiproliferative activity. The highest cytotoxic activity has been determined for compound 5 (IC50=10.16 μM) and the antiproliferative capacity of the compounds was found to be in the following order: 5>3d>3f>3e>3b>6>3a>3c. Among all synthesized compounds, only the 3d, 3f and 5 possessed higher cytotoxic activity then their starting compound 1. Distinct activities of these new products depend on their different compositions. Furthermore, it may be suggested that these factors are directly to or may even be prominent contributors of antiproliferative effects.

Figure 2 Antiproliferative effect of the samples on HeLa cells. [3a: P<0.0001, R2=0.943; 3b: P<0.0001, R2=0.922; 3c: P<0.0001, R2=0.945; 3d: P<0.0001, R2=0.964; 3e: P<0.0001, R2=0.956; 3f: P<0.0001, R2=0.945; 5: P<0.0001, R2=0.911; 6: P<0.0001, R2=0.934. Starting compound 1: P<0.0001, R2=0.982. Data are mean ±SD of percent changes compared with untreated controls (n=9)].
Figure 2

Antiproliferative effect of the samples on HeLa cells. [3a: P<0.0001, R2=0.943; 3b: P<0.0001, R2=0.922; 3c: P<0.0001, R2=0.945; 3d: P<0.0001, R2=0.964; 3e: P<0.0001, R2=0.956; 3f: P<0.0001, R2=0.945; 5: P<0.0001, R2=0.911; 6: P<0.0001, R2=0.934. Starting compound 1: P<0.0001, R2=0.982. Data are mean ±SD of percent changes compared with untreated controls (n=9)].

Synthetic amino- and thiolated naphthoquinones have been investigated for their cytotoxic activities for many years [12] and as the amino derivatization has been found to enhance biological activity in most cases,

several aminoquinones have been synthesized. The compounds 3a-f obtained in this study share a common core structure with those synthesized by Pal et al. [29] except the R side chains (Figure 1). Some derivatives of 2-chloro-3-(n-alkylamino)-1,4-naphthoquinones (n-alkyl: methyl, ethyl, propyl and butyl) were found to possess antiproliferative effect on COLO205 (human colorectal adenocarcinoma) and MIAPaCa2 (human pancreatic carcinoma) cell lines whereas no activity was detected on 487MG (human primary glioblastoma) cell line [29]. Thus, in their study, it has been shown that length of the carbon chain in R group has an effect on the activity. The optimal structure of the alkyl group for the activity on COLO205 (IC50= 92.2 μM) and MIAPaCa2 (IC50= 12.8 μM) was found as -C3H7 and as -C2H5, respectively. The antiproliferative activity of all amino derivatives tested here on HeLa cells is higher than that of alkyl derivatives on COLO205 cells, although they have more complex structures on their side chains. However, only the antiproliferative effect of NH-substituted naphthoquinone derivative 3d (IC50= 12.82 μM) on HeLa cells seemed to compete with the effect of L1 (IC50= 11.5 μM) and L2 (IC50= 12.8 μM) on MIAPaCa2 cells [29] as their IC50 doses were very close (Table 1).

Table 1

The half maximal inhibitory concentration (IC50) of the compounds.

CompoundIC50 value
117.91 μM
3a47.86 μM
3b22.54 μM
3c52.97 μM
3d12.82 μM
3e21.53 μM
3f16.71 μM
510.16 μM
637.33 μM

As the reports related to antiproliferative effects of similar compounds are not common in the literature, we also searched the activity of starting compound 1 on HeLa cells, to understand the effect of derivatization on the activity. Previously the IC50 dose of 1,4-naphthoquinone on HeLa cells was found as 7.8 μM [33]. This result could not be interpreted as the incubation time was 72 hours whereas it was 48 hours in this study. Although this compound seems to be effective on HeLa cells as well as on the other cancer cell lines, 3d seems to be capable to compete with it. Moreover, 2,3-disubstituted-1,4-naphthoquinone derivatives obtained in this study may exhibit cell-specific or enhanced cytotoxic activities and other biological activities.

On the other hand, as a thiolated naphthoquinone derivative, compound 5 has the highest inhibitory activity among the all compounds tested here. The IC50 value of this compound having relatively simple side chain is 10.16 μM. This result indicated that mono-thiosubstitution enhanced the cytotoxicity. Thus, this compound may be a good candidate for further studies, such as understanding the effects on other cancer cell lines, revealing the action mechanism, and in vivo tests.

4 Conclusion

In this paper, we have described the synthesis and structural characterization of some N(H)-, S- and S,S-substituted-1,4-naphthoquinones. The new compounds were characterized by UV-Vis, 1H and 13C NMR, MS (ESI), FT-IR, and their antiproliferative effects were investigated against HeLa cells. Our results indicated that the new naphthoquinone compounds, especially 5 and 3d might be suggested as potent inhibitors of HeLa cells. But, further work are needed to check their other activities related to anticancer effect, cell specificity, action mechanism and in vivo efficacy. Derivatization strategies carried out here might be helpful to get new N(H)-, S- and S,S-substituted-1,4-naphthaquinones with better antiproliferative activity. When the antiproliferative effects of these compounds were determined against human cervical cancer, it was shown that all compounds have antiproliferative properties. In the light of the findings of this study, these new naphthoquinone compounds might be regarded as potential anticancer drugs which could be used in the health and pharmaceutical areas.

Acknowledgments

The authors would like to express their gratitude to Scientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa for financial support (Project Numbers: 36017, YADOP-32026).

  1. Conflict of interest: Authors declare no conflict of interest.

References

[1] Hussain H, Krohn K, Ahmad V.U., Miana G.A., Greend I.R., Lapachol: an overview, Arkivoc., 2007, ii, 145-171.10.3998/ark.5550190.0008.204Suche in Google Scholar

[2] Tandon V.K., Maurya H.K., Verma M.K., Kumar R., Shukla P.K., 'On water' assisted synthesis and biological evaluation of nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents, Eur. J. Med. Chem., 2010, 45, 2418-2426.10.1016/j.ejmech.2010.02.023Suche in Google Scholar

[3] Papageorgiou V.P., Assimopoulou A.N., Couladouros E. A., Hepworth D., Nicolaou K.C., The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products, Angew. Chem. Int. Ed., 1999, 38, 270-300.10.1002/(SICI)1521-3773(19990201)38:3<270::AID-ANIE270>3.0.CO;2-0Suche in Google Scholar

[4] Opitz W., Pelster B., Fruchtmann R., Krupka U., Gauss W., Kiehne H., et al., Dec. 1986, 1,4-Naphthoquinone derivatives having anti-inflammatory action, U.S. Patent 4,628,062,Suche in Google Scholar

[5] Hayashi T., Smith F.T., Lee K-H., Antitumor agents. 89. Psychorubrin, a new cytotoxic naphthoquinone from Psychotria rubra and its structure-activity relationships, J. Med. Chem., 1987, 30(11), 2005-2008.10.1021/jm00394a013Suche in Google Scholar

[6] Song G-Y., Kim Y., Zheng X-G., You Y.J., Cho H., Chung J.H., et al., Naphthazarin derivatives (IV): synthesis, inhibition of DNA topoisomerase I and cytotoxicity of 2- or 6-acyl-5,8-dimethoxy-1,4-naphthoquinones, Eur. J. Med. Chem., 2000, 35(3), 291298.10.1016/S0223-5234(00)00129-XSuche in Google Scholar

[7] Niculescu V-C., Muresan N., Salageanu A., Tucureanu C., Marinescu G., Chirigiu L., et al., Novel 2,3-disubstituted 1,4-naphthoquinone derivatives and their metal complexes - synthesis and in vitro cytotoxic effect against mouse fibrosarcoma L929 cells, J. Organomet. Chem., 2012, 700, 13-19.10.1016/j.jorganchem.2011.10.036Suche in Google Scholar

[8] Francisco A.I., Casellato A., Neves A.P., Carneiro J.W. de M., Vargas M.D., Visentin L. do C, et al., Novel 2-(R-phenyl) amino-3-(2-methylpropenyl)-[1,4]-naphthoquinones: synthesis, characterization, electrochemical behavior and antitumor activity, J. Braz. Chem., 2010, 21(1), 169-178.10.1590/S0103-50532010000100024Suche in Google Scholar

[9] Kim B.H., Yoo J., Park S-H., Jung J-K., Cho H., Chung Y. Synthesis and evaluation of antitumor activity of novel 1,4-naphthoquinone derivatives (IV), Arch. Pharm. Res., 2006, 29(2), 123-130.10.1007/BF02974272Suche in Google Scholar

[10] Kapadia G.J., Balasubramanian V., Tokuda H., Konoshima T., Takasaki M., Koyama J., et al., Anti-tumor promoting effects of naphthoquinone derivatives on short term Epstein-Barr early antigen activation assay and in mouse skin carcinogenesis, Cancer Lett.,, 1997, 113, 47-53.10.1016/S0304-3835(96)04582-XSuche in Google Scholar

[11] Silva T.M.S., Camara C.A., Barbosa T.P., Soares A.Z., da Cunha L.C., Pinto A.C., et al., Molluscicidal activity of synthetic lapachol amino and hydrogenated derivatives, Bioorg. Med. Chem., 2005, 13(1), 193-196.10.1016/j.bmc.2004.09.043Suche in Google Scholar

[12] Wellington K.W., Understanding cancer and anticancer activities of naphthoquinones-a review, RSC. Adv., 2015, 5, 20309-20338.10.1039/C4RA13547DSuche in Google Scholar

[13] Bhasin D., Chettiar S.N., Etter J.P., Mok M., Li P-K., Anticancer activity and SAR studies of substituted 1,4-naphthoquinones, Bioorg. Med. Chem., 2013, 21(15), 4662-4669.10.1016/j.bmc.2013.05.017Suche in Google Scholar

[14] Paengsri W., Baramee A., Synthesis and evaluation of anti-tuberculosis and anti-cancer activities of hydroxynaphthoquinone derivatives, Chiang. Mai. J. Sci., 2013, 40(1), 70-76.Suche in Google Scholar

[15] Stasevych M.V., Chervetsova V.G., Plotnikov M.Yu., Platonov M.O., Sabat S.I., Musyanovych R.Ya., et al., Synthesis and antimicrobial evaluation of novel 2-substituted-3-mercapto-1,4-naphthoquinones, Ukr. Bioorg. Acta., 2006, 2, 33-39.Suche in Google Scholar

[16] Prescott B., Potential antimalarial agents. Dervatives of 2-chloro-1,4-naphthoquinone, J. Med. Chem., 1969, 12, 181182.10.1021/jm00301a053Suche in Google Scholar

[17] Lin T.S., Zhu L.Ya., Xu S-P., Divo A.A., Sartorelli A.C., Synthesis and antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives, J. Med. Chem., 1991, 34(5), 1634–1639.10.1021/jm00109a016Suche in Google Scholar

[18] Nowicka B., Kruk J., Occurrence, biosynthesis and function of isoprenoid quinones, Biochim. Biophys. Acta., 2010, 1797, 1587–1605.10.1016/j.bbabio.2010.06.007Suche in Google Scholar

[19] Porter R.F., Rees W.W., Frauenglass E., Wilgus H.S., Nawn, G.H., Chiesa P.P., et al., The Chemistry of thioether-substituted hydroquinones and quinones. I. The 1,4-addition of a heterocyclic mercaptan to quinones. J. Org. Chem., 1964, 29(3), 588-594.10.1021/jo01026a017Suche in Google Scholar

[20] Xu K., Xiao Z., Tang Y.B., Huang L., Chen C-H., Ohkoshi E., Design and synthesis of naphthoquinone derivatives as antiproliferative agents and 20S proteasome inhibitors, Bioorg. Med. Chem. Lett., 2012, 22(8), 2772-2774.10.1016/j.bmcl.2012.02.086Suche in Google Scholar

[21] Brandy Y., Brandy N., Akinboye E., Lewis M., Mouamba C., Mack S., et al., Synthesis and characterization of novel unsymmetrical and symmetrical 3-halo- or 3-methoxy-substituted 2-dibenzoylamino-1,4-naphthoquinone derivatives, Molecules., 2013, 18(2), 1973-1984.10.3390/molecules18021973Suche in Google Scholar

[22] Moon C-K., Ryu C-K., Aug. 1997, 2-Chloro-3-arylamino-1,4-naphthoquinone derivatives, process for preparation thereof and use thereof as an agent for inhibiting platelet aggregation, U.S. Patent 5654321,Suche in Google Scholar

[23] Ryu C-K., Choi K.U., Shim J-Y., You H-J., Choi I.H., Chae M.J., Synthesis and antifungal activity of 6-arylthio-/6-Arylamino-4,7-dioxobenzothiazoles, Bioorg. Med. Chem., 2003, 11 (18), 4003-4008.10.1016/S0968-0896(03)00390-0Suche in Google Scholar

[24] Ryu C-K., Kang H-Y., Yi Y-J., Shin K-H., Lee B-H., Synthesis and antifungal activities of 5/6-arylamino-4,7-dioxobenzothiazoles, Bioorg. Med. Chem. Lett., 2000, 10(14), 1589-1591.10.1016/S0960-894X(00)00301-2Suche in Google Scholar

[25] Ryu C-K., Sun Y-J., Shim J-Y., You H-J., Choi K.U., Lee H., Synthesis and antifungal activity of 6,7-bis-[s-(aryl)thio]-5,8-quinolinediones, Arch. Pharm. Res., 2002, 25(6), 795-800.10.1007/BF02976994Suche in Google Scholar

[26] Bernardo P.H., Chai C.L.L., Le Guen M., Smith G.D., Waring P., Structure-activity delineation of quinones related to the biologically active Calothrixin B, Bioorg. Med. Chem. Lett., 2007, 17(1), 82-85.10.1016/j.bmcl.2006.09.090Suche in Google Scholar

[27] Tomasz M., Mitomycin C: small, fast and deadly (but very selective) Chem. Biol., 1995, 2(9), 575-579.10.1016/1074-5521(95)90120-5Suche in Google Scholar

[28] Szybalski W., Iyer V.N., Crosslinking of DNA by enzymatic or activated mitomycin and porfiromycins, bifunctionally alkylating antibiotics. Feder Proc. 1964, 23, 946–957.Suche in Google Scholar

[29] Pal S., Jadhav M., Weyhermüller T., Patil Y., Nethaji M., Kasabe U., et al., Molecular structures and antiproliferative activity of side-chain saturated and homologated analogs of 2-chloro-3-(n-alkylamino)-1,4-napthoquinone, J. Mol. Struct., 2013, 1049, 355-361.10.1016/j.molstruc.2013.06.062Suche in Google Scholar

[30] Shit M.M., Kugelmant A., Iwamoto T., Tiant L., Forman H.J., Quinone-induced oxidative stress elevates glutathione and induces y-Glutamylcysteine synthetase activity in rat lung epithelial L2 cells, J. Biol. Chem., 1994, 269(42), Issue of October 21, 26512-26517.10.1016/S0021-9258(18)47224-9Suche in Google Scholar

[31] Tandon V.K., Singh R.V., Yadav, D.B., Synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antiviral, antifungal and anticancer agents, Bioorg. Med. Chem. Lett., 2004, 14, 2901–2904.10.1016/j.bmcl.2004.03.047Suche in Google Scholar

[32] Itoigawa M., Ito C., Tan H.T-W., Okuda M., Tokuda H., Nishino H., et al., Cancer chemopreventive activity of naphthoquinones and their analogs from avicennia plants, Cancer Lett., 2001, 174, 135-139.10.1016/S0304-3835(01)00707-8Suche in Google Scholar

[33] Kayashima T., Mori M., Yoshida H., Mizushina Y., Matsubara K., 1,4-Naphthoquinone is a potent inhibitor of human cancer cell growth and angiogenesis, Cancer Lett., 2009, 278, 34-40.10.1016/j.canlet.2008.12.020Suche in Google Scholar PubMed

[34] Kongkathip N., Pradidphol N., Hasitapan K., Kongkathip B., Synthesis and anticancer evaluation of naphthoquinone esters with 2'-cyclopentyl and 2'-cyclohexyl substituents, Biosci., Biotechnol. Biochem., 2010, 74(6), 1205-1214.10.1271/bbb.90946Suche in Google Scholar PubMed

[35] Sayil C., Ibis C., Synthesis and spectral properties of 1,4-naphthoquinone sulfanyl derivatives, Russ. J. Org. Chem., 2010, 46(2), 209-215.10.1134/S1070428010020119Suche in Google Scholar

[36] Sayil C., Deniz N.G., Cinarli A., Synthesis of N-, S-, O-substituted quinone dyes and their dyeability on polyester fibers, Prog. Org. Coat., 2016, 98, 39-42.10.1016/j.porgcoat.2016.04.017Suche in Google Scholar

[37] Sayil C., Kurban S., Ibis C., Synthesis and characterization of nitrogen and sulfur containingl,4-naphthoquinones, Phosphorus. Sulfur. Silicon. Relat. Elem., 2013, 188, 1855-1867.10.1080/10426507.2013.796475Suche in Google Scholar

[38] Deniz N.G., Ozyurek M., Tufan A.N., Apak R., One-pot synthesis, characterization, antioxidant capacity of sulfur and oxygen substituted 1,4-naphthoquinones and a structural study, Monatsh. Chem., 2015, 146, 2117-2126.10.1007/s00706-015-1517-5Suche in Google Scholar

[39] Deniz N.G., Ibis C., Gokmen Z., Stasevych M., Novikov V., Komarovska- Porokhnyavets O., et al., Design, synthesis, biological evaluation, and antioxidant and cytotoxic activity of heteroatom-substituted 1,4-naphtho- and benzoquinones, Chem. Pharm. Bull., 2015, 63(12), 1029-1039.10.1248/cpb.c15-00607Suche in Google Scholar

[40] Ibis C., Yildiz M., Sayil C., The Synthesis of novel mono(alkoxy)-, tris(thio)- and tetrakis(thio)-substituted quinones from the reactions of p-chloranil with various S-nucleophiles, Bull. Korean. Chem. Soc., 2009, 30(10), 2381-2386.10.1002/chin.201013083Suche in Google Scholar

[41] Sayil C., Ibis C., Synthesis and spectral properties of novel thionaphtoquinone dyes, Bull. Korean. Chem. Soc., 2010, 31(5), 1233-1236.10.5012/bkcs.2010.31.5.1233Suche in Google Scholar

[42] Tjepkema J.J., Preparation of alkylthio-substituted 1,4-naphthoquinones and p-benzoquinones, Recl. Trav. Chim. Pays-Bas. Belg., 1952, 71(9), 853-856.10.1002/recl.19520710903Suche in Google Scholar

[43] Onay-Ucar E., Erol O., Kandemir B., Mertoglu E., Karagoz A., Arda N., Viscum album L. extracts protects HeLa cells against nuclear and mitochondrial DNA damage, J. Evid. Based. Complementary. Altern. Med., 2012, Article ID 958740, 7 pages,10.1155/2012/958740Suche in Google Scholar

[44] Mosmann T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, J. Immunol. Method., 1983, 65(1-2), 55-63.10.1016/0022-1759(83)90303-4Suche in Google Scholar

Received: 2018-11-20
Accepted: 2019-01-08
Published Online: 2019-04-24

© 2019 Aysecik Kacmaz et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 Public License.

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  104. Impact of xanthan gum addition on phenolic acids composition and selected properties of new gluten-free maize-field bean pasta
  105. Impact of storage temperature and time on Moldavian dragonhead oil – spectroscopic and chemometric analysis
  106. The effect of selected substances on the stability of standard solutions in voltammetric analysis of ascorbic acid in fruit juices
  107. Determination of the content of Pb, Cd, Cu, Zn in dairy products from various regions of Poland
  108. Special Issue on IC3PE 2018 Conference
  109. The Photocatalytic Activity of Zns-TiO2 on a Carbon Fiber Prepared by Chemical Bath Deposition
  110. N-octyl chitosan derivatives as amphiphilic carrier agents for herbicide formulations
  111. Kinetics and Mechanistic Study of Hydrolysis of Adenosine Monophosphate Disodium Salt (AMPNa2) in Acidic and Alkaline Media
  112. Antimalarial Activity of Andrographis Paniculata Ness‘s N-hexane Extract and Its Major Compounds
  113. Special Issue on ABB2018 Conference
  114. Special Issue on ICCESEN 2017
  115. Theoretical Diagnostics of Second and Third-order Hyperpolarizabilities of Several Acid Derivatives
  116. Determination of Gamma Rays Efficiency Against Rhizoctonia solani in Potatoes
  117. Studies On Compatibilization Of Recycled Polyethylene/Thermoplastic Starch Blends By Using Different Compatibilizer
  118. Liquid−Liquid Extraction of Linalool from Methyl Eugenol with 1-Ethyl-3-methylimidazolium Hydrogen Sulfate [EMIM][HSO4] Ionic Liquid
  119. Synthesis of Graphene Oxide Through Ultrasonic Assisted Electrochemical Exfoliation
  120. Special Issue on ISCMP 2018
  121. Synthesis and antiproliferative evaluation of some 1,4-naphthoquinone derivatives against human cervical cancer cells
  122. The influence of the grafted aryl groups on the solvation properties of the graphyne and graphdiyne - a MD study
  123. Electrochemical modification of platinum and glassy carbon surfaces with pyridine layers and their use as complexing agents for copper (II) ions
  124. Effect of Electrospinning Process on Total Antioxidant Activity of Electrospun Nanofibers Containing Grape Seed Extract
  125. Effect Of Thermal Treatment Of Trepel At Temperature Range 800-1200˚C
  126. Topical Issue on Agriculture
  127. The effect of Cladophora glomerata exudates on the amino acid composition of Cladophora fracta and Rhizoclonium sp.
  128. Influence of the Static Magnetic Field and Algal Extract on the Germination of Soybean Seeds
  129. The use of UV-induced fluorescence for the assessment of homogeneity of granular mixtures
  130. The use of microorganisms as bio-fertilizers in the cultivation of white lupine
  131. Lyophilized apples on flax oil and ethyl esters of flax oil - stability and antioxidant evaluation
  132. Production of phosphorus biofertilizer based on the renewable materials in large laboratory scale
  133. Human health risk assessment of potential toxic elements in paddy soil and rice (Oryza sativa) from Ugbawka fields, Enugu, Nigeria
  134. Recovery of phosphates(V) from wastewaters of different chemical composition
  135. Special Issue on the 4th Green Chemistry 2018
  136. Dead zone for hydrogenation of propylene reaction carried out on commercial catalyst pellets
  137. Improved thermally stable oligoetherols from 6-aminouracil, ethylene carbonate and boric acid
  138. The role of a chemical loop in removal of hazardous contaminants from coke oven wastewater during its treatment
  139. Combating paraben pollution in surface waters with a variety of photocatalyzed systems: Looking for the most efficient technology
  140. Special Issue on Chemistry Today for Tomorrow 2019
  141. Applying Discriminant and Cluster Analyses to Separate Allergenic from Non-allergenic Proteins
  142. Chemometric Expertise Of Clinical Monitoring Data Of Prolactinoma Patients
  143. Chemomertic Risk Assessment of Soil Pollution
  144. New composite sorbent for speciation analysis of soluble chromium in textiles
  145. Photocatalytic activity of NiFe2O4 and Zn0.5Ni0.5Fe2O4 modified by Eu(III) and Tb(III) for decomposition of Malachite Green
  146. Photophysical and antibacterial activity of light-activated quaternary eosin Y
  147. Spectral properties and biological activity of La(III) and Nd(III) Monensinates
  148. Special Issue on Monitoring, Risk Assessment and Sustainable Management for the Exposure to Environmental Toxins
  149. Soil organic carbon mineralization in relation to microbial dynamics in subtropical red soils dominated by differently sized aggregates
  150. A potential reusable fluorescent aptasensor based on magnetic nanoparticles for ochratoxin A analysis
  151. Special Issue on 13th JCC 2018
  152. Fluorescence study of 5-nitroisatin Schiff base immobilized on SBA-15 for sensing Fe3+
  153. Thermal and Morphology Properties of Cellulose Nanofiber from TEMPO-oxidized Lower part of Empty Fruit Bunches (LEFB)
  154. Encapsulation of Vitamin C in Sesame Liposomes: Computational and Experimental Studies
  155. A comparative study of the utilization of synthetic foaming agent and aluminum powder as pore-forming agents in lightweight geopolymer synthesis
  156. Synthesis of high surface area mesoporous silica SBA-15 by adjusting hydrothermal treatment time and the amount of polyvinyl alcohol
  157. Review of large-pore mesostructured cellular foam (MCF) silica and its applications
  158. Ion Exchange of Benzoate in Ni-Al-Benzoate Layered Double Hydroxide by Amoxicillin
  159. Synthesis And Characterization Of CoMo/Mordenite Catalyst For Hydrotreatment Of Lignin Compound Models
  160. Production of Biodiesel from Nyamplung (Calophyllum inophyllum L.) using Microwave with CaO Catalyst from Eggshell Waste: Optimization of Transesterification Process Parameters
  161. The Study of the Optical Properties of C60 Fullerene in Different Organic Solvents
  162. Composite Material Consisting of HKUST-1 and Indonesian Activated Natural Zeolite and its Application in CO2 Capture
  163. Topical Issue on Environmental Chemistry
  164. Ionic liquids modified cobalt/ZSM-5 as a highly efficient catalyst for enhancing the selectivity towards KA oil in the aerobic oxidation of cyclohexane
  165. Application of Thermal Resistant Gemini Surfactants in Highly Thixotropic Water-in-oil Drilling Fluid System
  166. Screening Study on Rheological Behavior and Phase Transition Point of Polymer-containing Fluids produced under the Oil Freezing Point Temperature
  167. The Chemical Softening Effect and Mechanism of Low Rank Coal Soaked in Alkaline Solution
  168. The Influence Of NO/O2 On The NOx Storage Properties Over A Pt-Ba-Ce/γ-Al2O3 Catalyst
  169. Special Issue on the International conference CosCI 2018
  170. Design of SiO2/TiO2 that Synergistically Increases The Hydrophobicity of Methyltrimethoxysilane Coated Glass
  171. Antidiabetes and Antioxidant agents from Clausena excavata root as medicinal plant of Myanmar
  172. Development of a Gold Immunochromatographic Assay Method Using Candida Biofilm Antigen as a Bioreceptor for Candidiasis in Rats
  173. Special Issue on Applied Biochemistry and Biotechnology 2019
  174. Adsorption of copper ions on Magnolia officinalis residues after solid-phase fermentation with Phanerochaete chrysosporium
  175. Erratum
  176. Erratum to: Sand Dune Characterization For Preparing Metallurgical Grade Silicon
https://doi.org/10.1515/chem-2019-0030
Schlagwörter für diesen Artikel
Quinones; Amines; Thiols; Antiproliferative activity; HeLa cell
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Artikel in diesem Heft

  1. Regular Articles
  2. Research on correlation of compositions with oestrogenic activity of Cistanche based on LC/Q-TOF-MS/MS technology
  3. Efficacy of Pyrus elaeagnifolia subsp. elaeagnifolia in acetic acid–induced colitis model
  4. Anti-inflammatory and antinociceptive features of Bryonia alba L.: As a possible alternative in treating rheumatism
  5. High efficiency liposome fusion induced by reducing undesired membrane peptides interaction
  6. Prediction of the Blood-Brain Barrier Permeability Using RP-18 Thin Layer Chromatography
  7. Phytic Acid Extracted from Rice Bran as a Growth Promoter for Euglena gracilis
  8. Development of a validated spectrofluorimetric method for assay of sotalol hydrochloride in tablets and human plasma: application for stability-indicating studies
  9. Topological Indices of Hyaluronic Acid-Paclitaxel Conjugates’ Molecular Structure in Cancer Treatment
  10. Thermodynamic properties of the bubble growth process in a pool boiling of water-ethanol mixture two-component system
  11. Critical Roles of the PI3K-Akt-mTOR Signaling Pathway in Apoptosis and Autophagy of Astrocytes Induced by Methamphetamine
  12. Characteristics of Stable Hydrogen and Oxygen Isotopes of Soil Moisture under Different Land Use in Dry Hot Valley of Yuanmou
  13. Specific, highly sensitive and simple spectrofluorimetric method for quantification of daclatasvir in HCV human plasma patients and in tablets dosage form
  14. Chromium-modified cobalt molybdenum nitrides as catalysts for ammonia synthesis
  15. Langerhans cell-like dendritic cells treated with ginsenoside Rh2 regulate the differentiation of Th1 and Th2 cells in vivo
  16. Identification of Powdery Mildew Blumeria graminis f. sp. tritici Resistance Genes in Selected Wheat Varieties and Development of Multiplex PCR
  17. Computational Analysis of new Degree-based descriptors of oxide networks
  18. The Use Of Chemical Composition And Additives To Classify Petrol And Diesel Using Gas Chromatography–Mass Spectrometry And Chemometric Analysis: A Uk Study
  19. Minimal Energy Tree with 4 Branched Vertices
  20. Jatropha seed oil derived poly(esteramide-urethane)/ fumed silica nanocomposite coatings for corrosion protection
  21. Calculating topological indices of certain OTIS interconnection networks
  22. Energy storage analysis of R125 in UIO-66 and MOF-5 nanoparticles: A molecular simulation study
  23. Velvet Antler compounds targeting major cell signaling pathways in osteosarcoma - a new insight into mediating the process of invasion and metastasis in OS
  24. Effects of Azadirachta Indica Leaf Extract, Capping Agents, on the Synthesis of Pure And Cu Doped ZnO-Nanoparticles: A Green Approach and Microbial Activity
  25. Aqueous Micro-hydration of Na+(H2O)n=1-7 Clusters: DFT Study
  26. A proposed image-based detection of methamidophos pesticide using peroxyoxalate chemiluminescence system
  27. Phytochemical screening and estrogenic activity of total glycosides of Cistanche deserticola
  28. Biological evaluation of a series of benzothiazole derivatives as mosquitocidal agents
  29. Chemical pretreatments of Trapa bispinosa's peel (TBP) biosorbent to enhance adsorption capacity for Pb(ll)
  30. Dynamic Changes in MMP1 and TIMP1 in the Antifibrotic Process of Dahuang Zhechong Pill in Rats with Liver Fibrosis
  31. The Optimization and Production of Ginkgolide B Lipid Microemulsion
  32. Photodynamic Therapy Enhanced the Antitumor Effects of Berberine on HeLa Cells
  33. Chiral and Achiral Enantiomeric Separation of (±)-Alprenolol
  34. Correlation of Water Fluoride with Body Fluids, Dental Fluorosis and FT4, FT3 –TSH Disruption among Children in an Endemic Fluorosis area in Pakistan
  35. A one-step incubation ELISA kit for rapid determination of dibutyl phthalate in water, beverage and liquor
  36. Free Radical Scavenging Activity of Essential Oil of Eugenia caryophylata from Amboina Island and Derivatives of Eugenol
  37. Effects of Blue and Red Light On Growth And Nitrate Metabolism In Pakchoi
  38. miRNA-199a-5p functions as a tumor suppressor in prolactinomas
  39. Solar photodegradation of carbamazepine from aqueous solutions using a compound parabolic concentrator equipped with a sun tracking system
  40. Influence of sub-inhibitory concentration of selected plant essential oils on the physical and biochemical properties of Pseudomonas orientalis
  41. Preparation and spectroscopic studies of Fe(II), Ru(II), Pd(II) and Zn(II) complexes of Schiff base containing terephthalaldehyde and their transfer hydrogenation and Suzuki-Miyaura coupling reaction
  42. Complex formation in a liquid-liquid extraction-chromogenic system for vanadium(IV)
  43. Synthesis, characterization (IR, 1H, 13C & 31P NMR), fungicidal, herbicidal and molecular docking evaluation of steroid phosphorus compounds
  44. Analysis and Biological Evaluation of Arisaema Amuremse Maxim Essential Oil
  45. A preliminary assessment of potential ecological risk and soil contamination by heavy metals around a cement factory, western Saudi Arabia
  46. Anti- inflammatory effect of Prunus tomentosa Thunb total flavones in LPS-induced RAW264.7 cells
  47. Collaborative Influence of Elevated CO2 Concentration and High Temperature on Potato Biomass Accumulation and Characteristics
  48. Methods of extraction, physicochemical properties of alginates and their applications in biomedical field – a review
  49. Characteristics of liposomes derived from egg yolk
  50. Preparation of ternary ZnO/Ag/cellulose and its enhanced photocatalytic degradation property on phenol and benzene in VOCs
  51. Influence of Human Serum Albumin Glycation on the Binding Affinities for Natural Flavonoids
  52. Synthesis and antioxidant activity of 2-methylthio-pyrido[3,2-e][1,2,4] triazolo[1,5-a]pyrimidines
  53. Comparative study on the antioxidant activities of ten common flower teas from China
  54. Molecular Properties of Symmetrical Networks Using Topological Polynomials
  55. Synthesis of Co3O4 Nano Aggregates by Co-precipitation Method and its Catalytic and Fuel Additive Applications
  56. Phytochemical analysis, Antioxidant and Antiprotoscolices potential of ethanol extracts of selected plants species against Echinococcus granulosus: In-vitro study
  57. Silver nanoparticles enhanced fluorescence for sensitive determination of fluoroquinolones in water solutions
  58. Simultaneous Quantification of the New Psychoactive Substances 3-FMC, 3-FPM, 4-CEC, and 4-BMC in Human Blood using GC-MS
  59. Biodiesel Production by Lipids From Indonesian strain of Microalgae Chlorella vulgaris
  60. Miscibility studies of polystyrene/polyvinyl chloride blend in presence of organoclay
  61. Antibacterial Activities of Transition Metal complexes of Mesocyclic Amidine 1,4-diazacycloheptane (DACH)
  62. Novel 1,8-Naphthyridine Derivatives: Design, Synthesis and in vitro screening of their cytotoxic activity against MCF7 cell line
  63. Investigation of Stress Corrosion Cracking Behaviour of Mg-Al-Zn Alloys in Different pH Environments by SSRT Method
  64. Various Combinations of Flame Retardants for Poly (vinyl chloride)
  65. Phenolic compounds and biological activities of rye (Secale cereale L.) grains
  66. Oxidative degradation of gentamicin present in water by an electro-Fenton process and biodegradability improvement
  67. Optimizing Suitable Conditions for the Removal of Ammonium Nitrogen by a Microbe Isolated from Chicken Manure
  68. Anti-inflammatory, antipyretic, analgesic, and antioxidant activities of Haloxylon salicornicum aqueous fraction
  69. The anti-corrosion behaviour of Satureja montana L. extract on iron in NaCl solution
  70. Interleukin-4, hemopexin, and lipoprotein-associated phospholipase A2 are significantly increased in patients with unstable carotid plaque
  71. A comparative study of the crystal structures of 2-(4-(2-(4-(3-chlorophenyl)pipera -zinyl)ethyl) benzyl)isoindoline-1,3-dione by synchrotron radiation X-ray powder diffraction and single-crystal X-ray diffraction
  72. Conceptual DFT as a Novel Chemoinformatics Tool for Studying the Chemical Reactivity Properties of the Amatoxin Family of Fungal Peptides
  73. Occurrence of Aflatoxin M1 in Milk-based Mithae samples from Pakistan
  74. Kinetics of Iron Removal From Ti-Extraction Blast Furnace Slag by Chlorination Calcination
  75. Increasing the activity of DNAzyme based on the telomeric sequence: 2’-OMe-RNA and LNA modifications
  76. Exploring the optoelectronic properties of a chromene-appended pyrimidone derivative for photovoltaic applications
  77. Effect of He Qi San on DNA Methylation in Type 2 Diabetes Mellitus Patients with Phlegm-blood Stasis Syndrome
  78. Cyclodextrin potentiometric sensors based on selective recognition sites for procainamide: Comparative and theoretical study
  79. Greener synthesis of dimethyl carbonate from carbon dioxide and methanol using a tunable ionic liquid catalyst
  80. Nonisothermal Cold Crystallization Kinetics of Poly(lactic acid)/Bacterial Poly(hydroxyoctanoate) (PHO)/Talc
  81. Enhanced adsorption of sulfonamide antibiotics in water by modified biochar derived from bagasse
  82. Study on the Mechanism of Shugan Xiaozhi Fang on Cells with Non-alcoholic Fatty Liver Disease
  83. Comparative Effects of Salt and Alkali Stress on Antioxidant System in Cotton (Gossypium Hirsutum L.) Leaves
  84. Optimization of chromatographic systems for analysis of selected psychotropic drugs and their metabolites in serum and saliva by HPLC in order to monitor therapeutic drugs
  85. Electrocatalytic Properties of Ni-Doped BaFe12O19 for Oxygen Evolution in Alkaline Solution
  86. Study on the removal of high contents of ammonium from piggery wastewater by clinoptilolite and the corresponding mechanisms
  87. Phytochemistry and toxicological assessment of Bryonia dioica roots used in north-African alternative medicine
  88. The essential oil composition of selected Hemerocallis cultivars and their biological activity
  89. Mechanical Properties of Carbon Fiber Reinforced Nanocrystalline Nickel Composite Electroforming Deposit
  90. Anti-c-myc efficacy block EGFL7 induced prolactinoma tumorigenesis
  91. Topical Issue on Applications of Mathematics in Chemistry
  92. Zagreb Connection Number Index of Nanotubes and Regular Hexagonal Lattice
  93. The Sanskruti index of trees and unicyclic graphs
  94. Valency-based molecular descriptors of Bakelite network BNmn
  95. Computing Topological Indices for Para-Line Graphs of Anthracene
  96. Zagreb Polynomials and redefined Zagreb indices of Dendrimers and Polyomino Chains
  97. Topological Descriptor of 2-Dimensional Silicon Carbons and Their Applications
  98. Topological invariants for the line graphs of some classes of graphs
  99. Words for maximal Subgroups of Fi24‘
  100. Generators of Maximal Subgroups of Harada-Norton and some Linear Groups
  101. Special Issue on POKOCHA 2018
  102. Influence of Production Parameters on the Content of Polyphenolic Compounds in Extruded Porridge Enriched with Chokeberry Fruit (Aronia melanocarpa (Michx.) Elliott)
  103. Effects of Supercritical Carbon Dioxide Extraction (SC-CO2) on the content of tiliroside in the extracts from Tilia L. flowers
  104. Impact of xanthan gum addition on phenolic acids composition and selected properties of new gluten-free maize-field bean pasta
  105. Impact of storage temperature and time on Moldavian dragonhead oil – spectroscopic and chemometric analysis
  106. The effect of selected substances on the stability of standard solutions in voltammetric analysis of ascorbic acid in fruit juices
  107. Determination of the content of Pb, Cd, Cu, Zn in dairy products from various regions of Poland
  108. Special Issue on IC3PE 2018 Conference
  109. The Photocatalytic Activity of Zns-TiO2 on a Carbon Fiber Prepared by Chemical Bath Deposition
  110. N-octyl chitosan derivatives as amphiphilic carrier agents for herbicide formulations
  111. Kinetics and Mechanistic Study of Hydrolysis of Adenosine Monophosphate Disodium Salt (AMPNa2) in Acidic and Alkaline Media
  112. Antimalarial Activity of Andrographis Paniculata Ness‘s N-hexane Extract and Its Major Compounds
  113. Special Issue on ABB2018 Conference
  114. Special Issue on ICCESEN 2017
  115. Theoretical Diagnostics of Second and Third-order Hyperpolarizabilities of Several Acid Derivatives
  116. Determination of Gamma Rays Efficiency Against Rhizoctonia solani in Potatoes
  117. Studies On Compatibilization Of Recycled Polyethylene/Thermoplastic Starch Blends By Using Different Compatibilizer
  118. Liquid−Liquid Extraction of Linalool from Methyl Eugenol with 1-Ethyl-3-methylimidazolium Hydrogen Sulfate [EMIM][HSO4] Ionic Liquid
  119. Synthesis of Graphene Oxide Through Ultrasonic Assisted Electrochemical Exfoliation
  120. Special Issue on ISCMP 2018
  121. Synthesis and antiproliferative evaluation of some 1,4-naphthoquinone derivatives against human cervical cancer cells
  122. The influence of the grafted aryl groups on the solvation properties of the graphyne and graphdiyne - a MD study
  123. Electrochemical modification of platinum and glassy carbon surfaces with pyridine layers and their use as complexing agents for copper (II) ions
  124. Effect of Electrospinning Process on Total Antioxidant Activity of Electrospun Nanofibers Containing Grape Seed Extract
  125. Effect Of Thermal Treatment Of Trepel At Temperature Range 800-1200˚C
  126. Topical Issue on Agriculture
  127. The effect of Cladophora glomerata exudates on the amino acid composition of Cladophora fracta and Rhizoclonium sp.
  128. Influence of the Static Magnetic Field and Algal Extract on the Germination of Soybean Seeds
  129. The use of UV-induced fluorescence for the assessment of homogeneity of granular mixtures
  130. The use of microorganisms as bio-fertilizers in the cultivation of white lupine
  131. Lyophilized apples on flax oil and ethyl esters of flax oil - stability and antioxidant evaluation
  132. Production of phosphorus biofertilizer based on the renewable materials in large laboratory scale
  133. Human health risk assessment of potential toxic elements in paddy soil and rice (Oryza sativa) from Ugbawka fields, Enugu, Nigeria
  134. Recovery of phosphates(V) from wastewaters of different chemical composition
  135. Special Issue on the 4th Green Chemistry 2018
  136. Dead zone for hydrogenation of propylene reaction carried out on commercial catalyst pellets
  137. Improved thermally stable oligoetherols from 6-aminouracil, ethylene carbonate and boric acid
  138. The role of a chemical loop in removal of hazardous contaminants from coke oven wastewater during its treatment
  139. Combating paraben pollution in surface waters with a variety of photocatalyzed systems: Looking for the most efficient technology
  140. Special Issue on Chemistry Today for Tomorrow 2019
  141. Applying Discriminant and Cluster Analyses to Separate Allergenic from Non-allergenic Proteins
  142. Chemometric Expertise Of Clinical Monitoring Data Of Prolactinoma Patients
  143. Chemomertic Risk Assessment of Soil Pollution
  144. New composite sorbent for speciation analysis of soluble chromium in textiles
  145. Photocatalytic activity of NiFe2O4 and Zn0.5Ni0.5Fe2O4 modified by Eu(III) and Tb(III) for decomposition of Malachite Green
  146. Photophysical and antibacterial activity of light-activated quaternary eosin Y
  147. Spectral properties and biological activity of La(III) and Nd(III) Monensinates
  148. Special Issue on Monitoring, Risk Assessment and Sustainable Management for the Exposure to Environmental Toxins
  149. Soil organic carbon mineralization in relation to microbial dynamics in subtropical red soils dominated by differently sized aggregates
  150. A potential reusable fluorescent aptasensor based on magnetic nanoparticles for ochratoxin A analysis
  151. Special Issue on 13th JCC 2018
  152. Fluorescence study of 5-nitroisatin Schiff base immobilized on SBA-15 for sensing Fe3+
  153. Thermal and Morphology Properties of Cellulose Nanofiber from TEMPO-oxidized Lower part of Empty Fruit Bunches (LEFB)
  154. Encapsulation of Vitamin C in Sesame Liposomes: Computational and Experimental Studies
  155. A comparative study of the utilization of synthetic foaming agent and aluminum powder as pore-forming agents in lightweight geopolymer synthesis
  156. Synthesis of high surface area mesoporous silica SBA-15 by adjusting hydrothermal treatment time and the amount of polyvinyl alcohol
  157. Review of large-pore mesostructured cellular foam (MCF) silica and its applications
  158. Ion Exchange of Benzoate in Ni-Al-Benzoate Layered Double Hydroxide by Amoxicillin
  159. Synthesis And Characterization Of CoMo/Mordenite Catalyst For Hydrotreatment Of Lignin Compound Models
  160. Production of Biodiesel from Nyamplung (Calophyllum inophyllum L.) using Microwave with CaO Catalyst from Eggshell Waste: Optimization of Transesterification Process Parameters
  161. The Study of the Optical Properties of C60 Fullerene in Different Organic Solvents
  162. Composite Material Consisting of HKUST-1 and Indonesian Activated Natural Zeolite and its Application in CO2 Capture
  163. Topical Issue on Environmental Chemistry
  164. Ionic liquids modified cobalt/ZSM-5 as a highly efficient catalyst for enhancing the selectivity towards KA oil in the aerobic oxidation of cyclohexane
  165. Application of Thermal Resistant Gemini Surfactants in Highly Thixotropic Water-in-oil Drilling Fluid System
  166. Screening Study on Rheological Behavior and Phase Transition Point of Polymer-containing Fluids produced under the Oil Freezing Point Temperature
  167. The Chemical Softening Effect and Mechanism of Low Rank Coal Soaked in Alkaline Solution
  168. The Influence Of NO/O2 On The NOx Storage Properties Over A Pt-Ba-Ce/γ-Al2O3 Catalyst
  169. Special Issue on the International conference CosCI 2018
  170. Design of SiO2/TiO2 that Synergistically Increases The Hydrophobicity of Methyltrimethoxysilane Coated Glass
  171. Antidiabetes and Antioxidant agents from Clausena excavata root as medicinal plant of Myanmar
  172. Development of a Gold Immunochromatographic Assay Method Using Candida Biofilm Antigen as a Bioreceptor for Candidiasis in Rats
  173. Special Issue on Applied Biochemistry and Biotechnology 2019
  174. Adsorption of copper ions on Magnolia officinalis residues after solid-phase fermentation with Phanerochaete chrysosporium
  175. Erratum
  176. Erratum to: Sand Dune Characterization For Preparing Metallurgical Grade Silicon
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