Home A new phenyl alkyl ester and a new combretin triterpene derivative from Combretum fragrans F. Hoffm (Combretaceae) and antiproliferative activity
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A new phenyl alkyl ester and a new combretin triterpene derivative from Combretum fragrans F. Hoffm (Combretaceae) and antiproliferative activity

  • Isaac Silvère Gade EMAIL logo , Corinne Chadeneau , Richard Tagne Simo , Emmanuel Talla , Alex De Theodore Atchade , Paule Seité , Brigitte Vannier , Sophie Laurent , Celine Henoumont , Armel H. Nwabo Kamdje and Jean-Marc Muller
Published/Copyright: December 31, 2020
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Open Chemistry
From the journal Open Chemistry Volume 18 Issue 1

Abstract

This work concerns the isolation and structure elucidation of compounds obtained from the extract of leaves and stem bark of Combretum fragrans F. Hoffm. Both extracts and some isolated compounds were tested for antiproliferative activity on glioblastoma (U87MG and C6 cells) and prostate (PC-3 cells) cancer cell lines using XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay. The dichloromethane/methanol (1:1) extract of the leaves led to the isolation of two new compounds such as fragransinate (1) and combretin C (2), alongside five known compounds such as combretin A (3), belamcanidin (4), cirsilineol (5), velutin (6), and a mixture of β-sitosterol-3-O-β-d-glucopyranoside (10a) and stigmasterol-3-O-β-d-glucopyranoside (10b), whereas the methanol extract of the stem bark led to the isolation of three known compounds betulinic acid (7), bellericagenin B (8), and a mixture of β-sitosterol (9a) and stigmasterol (9b). The structure of compounds was elucidated by nuclear magnetic resonance and mass spectrometry data. The methanol extract of the stem bark showed a powerful antiproliferative activity on all tested cells, as well as the extract of leaves which also showed important cytotoxicity effect. Compound (3) showed good antiproliferative activity particularly on U87MG and PC-3 cells, whereas compound (5) exhibits moderated activity. Compounds (2) and (8) were not active on all tested cells.

Keywords: Combretum fragrans F. Hoffm; fragransinate; combretin C; antiproliferative activity

1 Introduction

The genus Combretum is the largest and most widespread genus of Combretaceae. It is widely distributed in tropical and subtropical regions (Africa, India, and China) and comprises about 200 and 250 species that include trees, shrubs, shrublets, or woody climbers [1]. The genus Combretum is reported to have various biological activities such as antioxidant, anti-inflammatory, antimalarial, antibacterial, and cytotoxicity against tumor cells [1,2]. Phytochemical studies of Combretum genus showed many secondary metabolites such as flavonoids, triterpenes, lignans, phenanthrenes, and stilbenoids. [1,2]. Combretum fragrans F. Hoffm (syn: Combretum adenogonium Steud. ex A. Rich) is a medicinal plant belonging to the Combretum genus. It is a shrub or a small tree that grows up to 10–12 m high. The plant is found in deciduous woodland, wooded grassland associated with seasonally waterlogged clay soils, and on shallow, stony soils [3]. C. fragrans F. Hoffm is used in African folk medicine for the treatment of various types of disease, such as coughs, syphilis, leprosy, septic wounds, fungal infection of the scalp, diarrhea, hypertension, incurable wound, malaria, snake bite, gonorrhea, pain, and inflammation [4,5,6]. In the northern part of Cameroon, the plant is used to treat jaundice, diabetic wound, ulcers, and cancers. Pharmacological investigation of C. fragrans F. Hoffm extracts have been established to have antibacterial, antifungal, and antiproliferative properties [7,8], whereas phytochemical analysis of leaves, stem bark, and roots has revealed the presence of flavonoids, triterpenes, sterols, saponins, and tannins [9,10]. Despite the well-documented benefits of C. fragrans F. Hoffm, only few phytochemical studies have been performed on it.

The search of novel bioactive compounds against cancer is still on, because many cancer patients develop resistance to the existing anticancer agents during treatment and because of the undesired side effects produced by these anticancer agents. Plants offer a large possibility to find novel anticancer agents with new mechanism of action and weak toxicological effect. It is in this sense that we investigated C. fragrans F. Hoffm. The present work describes the isolation of compounds from extract of leaves and stem bark of C. fragrans F. Hoffm and evaluation of antiproliferative activity of both extracts and some isolated compounds on glioblastoma (GBM) and prostate cancer cell lines.

2 Materials and methods

2.1 General experimental procedure

The melting point of the new compounds was recorded in an open capillary using Electrothermal 9100 and is uncorrected. IR spectra were recorded on FT-IR spectrometer (Perkin-Elmer Spectrum 100). The proton and 13carbon nuclear magnetic resonance (NMR) data were recorded on spectrometer Bruker Avance AV-500 and 600, and tetramethylsilane (TMS) was used as standard. Chemical shifts are given in ppm (δ) and coupling constant (J) in Hz. CDCl3, MeOD, and DMSO-d6 were used as NMR solvents. Electrospray ionization-mass spectrometry (ESI-MS) spectra were registered on a QTOF Spectrometer (Bruker, Germany) equipped with a ZQ F1 source. The spectrometer was operated in positive mode (scan: 150–1,500; centroid CV = 20). The high resolution mass spectrum was registered on LC-MS-QTOF Spectrometer (Bruker, Germany) equipped with ESI source operating in positive mode. Column chromatography (CC) was performed on silica gel 60 (70–230 mesh, Merck), and thin layer chromatography was performed on silica gel precoated plates F-254 Merk (20 × 20 cm). Spots were visualized under UV light (254 and 365 nm), sprayed with 5% of phosphomolybdic acid prepared in ethanol, then heated. XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) reagent from Promega was used to evaluate antiproliferatve activity.

2.2 Plant material

Leaves and stem bark of C. fragrans F. Hoffm were collected during the month of May 2017 at Padarmé located in Bibémi subdivision, in the north region of Cameroon. The sample was identified at the National Herbarium of Cameroon, where a voucher specimen is deposited under the number 39,753/HNC.

2.3 Extraction and isolation

The powders of 1 kg of leaves and 1 kg of stem bark of C. fragrans F. Hoffm were extracted separately by maceration at room temperature with 5 L of dichloromethane/methanol (CH2Cl2/MeOH) (1:1) and methanol (MeOH) respectively for 48 h with intermittent stirring. After filtration on Whatman filter paper, the resulting solutions were concentrated using a rotary evaporator. The procedure was repeated thrice to optimize extraction. We obtained 55 g of crude extract from the leaves and 40 g from the stem bark. Then, a quantity of 30 g of each crude extract was taken differently and each subjected to CC separation on silica gel with the gradient eluting system hexane–ethyl acetate (100:0 → 0:100), followed by ethyl acetate–methanol (100:0 → 0:100). The fractions of 100 mL each were collected and concentrated on rotary evaporator. From the extract of leaves, two new compounds, fragransinate (1, 5.1 mg) and combretin C (2, 215 mg), alongside four known compounds combretin A (3, 46 mg), belamcanidin (4, 12.3 mg), cirsilineol (5, 64 mg), and velutin (6, 60 mg), and a mixture of β-sitosterol-3-O-β-d-glupyranoside and stigmasterol-3-O-β-d-glucopyranoside (10a,b, 9 mg) were isolated. From the methanol crude extract of the stem bark, three known compounds: betulinic acid (7, 4.3 mg), bellericagenin B (8, 13 mg), and a mixture of β-sitosterol and stigmasterol (9a, b, 15.6 mg) were isolated (Figure 1).

Figure 1 Chemical structures of compounds isolated from Combretum fragrans F. Hoffm.
Figure 1

Chemical structures of compounds isolated from Combretum fragrans F. Hoffm.

2.3.1 Compound 1: fragransinate (3ʹ-(3″,4″-dihydroxy-5-methoxyphenyl)propyl heptadecanoate)

Whitish solid; C27H46O5; m.p. = 66.5–67.5; IR: νmax = 3,400 cm−1 (–OH), 1,735 cm−1 (C═O), 1,450–1,600 cm−1 (aromatic ring), 1,100 and 1,150 cm−1 (C–O); (+) ESI-MS m/z 496 [M + 2Na]+; 1H and 13C NMR data, see Table 1.

Table 1

1H and 13C NMR data for compounds 1 (CDCl3,δ in ppm, 600 and 151 MHz)

No.1
δH (Mult., J(Hz))δC
1—174.0
22.33 (t, j = 7.5; 2H)34.4
31.64 (dd, j = 7.5, 14.2; 2H)25.0
4–161.73–1.22 (m)29.2–29.7
170.90 (t, j = 6.9; 3H)14.1
1ʹ4.10 (t, j = 6.5; 2H)63.5
2ʹ1.93 (dd, j = 7.6, 6.5; 2H)32.1
3ʹ2.60 (t, j = 7.6 Hz; 2H)30.3
1″—133.1
2″6.30 (s, 1H)103.2
3″—146.7
4″—130.5
5″—143.7
6″6.45 (s, 1H)108.3
MeO–3.89 (s, 3H)56.11

2.3.2 Compounds 2: combretin C (3-(β-d-xylopyranosyl)-15α-hydroxycycloartan-28-oic acid)

White powder; C36H60O8; m.p. = 239.1–240.1; IR: νmax = 3,400 cm−1 (–OH), 1,700 cm−1 (C═O) and 1,000–1,025 cm−1 (C–O); High resolution ESI mass spectrum (HRESI-MS) (+) HRESI-MS m/z 643.4149 [M + Na]+ (calculated for C36H60O8, 643.4288); 1H and 13C NMR data, see Table 2.

Table 2

1H and 13C NMR data for compounds 2 (DMSO-d6, δ in ppm, 500 and 126 MHz)

No.2
δH (Mult., J(Hz))δC
11.24a, 1.08a32.3
21.81a, 1.52a28.5
33.96 (dd, j = 11.0, 4.7; 1H)82.4
4—58.8
51.92a44.7
61.58a, 1.15a24.6
727.6
846.9
9—19.3
10—26.0
1127.1
1234.7
13—48.3
14—44.6
153.24 (m, 1H)71.2
161.85a43.9
171.57a51.5
181.01 (s, 3H)18.9
190.35 (d, j = 4.0; H-19b), 0.54 (d, j = 4.0; H-19a)28.8
201.32a38.9
210.81 (d, 3H)18.6
221.71a, 1.24a34.9
2330.8
2435.1
252.2036.2
260.86 (brd, 3H)25.7
270.86 (brd, 3H)25.0
28—177.9
291.03 (s, 3H)10.0
300.9 S (s, 3H)14.3
311.00 (brd, 3H)18.6
Xylose
14.14 (d, j = 7.5; 1H)104.0
22.89 (brdd, 1H)73.4
33.02 (brdd, 1H)76.3
43.23 (brdd, 1H)69.4
53.65 (brdd, Ha-5ʹ); 2.97 (brdd, Hb-5ʹ)65.5
  1. a

    Signals overlapped.

2.4 Biological evaluation

2.4.1 Cell culture and cell conditions

The U87 human GBM cells line and C6 rat GBM cells line were maintained in Dulbecco’s modified Eagle’s medium (DMEM, 1 g/L glucose) with GlutaMAX™ (Gibco) and sodium pyruvate (Invitrogen), supplemented with 10% of fetal calf serum and 100 U/mL penicillin and 100 µg/mL streptomycin (Gibco) (antibiotics mixture). The PC-3 human prostate cancer cells line were maintained in the same condition except the use of DMEM medium with 4.5 g/L glucose. Cell cultures were carried out in a biological safety cabinet (laminar flow hood). An inverted microscope (OCO-2-KERN) was used for cell counting. All cells line were grown in a humidified incubator (95% air and 5% CO2) at 37°C.

2.4.2 Antiproliferative assay

The antiproliferative activity of extracts and some isolated compounds was evaluated using XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) test [11]. The assay is based on the reduction of XTT reagent (Promega) into an orange formazan dye by the metabolically active living cells. Thus, the U87 and C6 GBM cells, as well as the PC-3 prostate cancer cells were plated in 96-well plates respectively at a density of 5 × 103, 3 × 103, and 4 × 103 cells per well in 100 µL of the corresponding medium. Then, cells were allowed to attach overnight in growth medium. After 24 h of incubation, the medium was removed and replaced with fresh medium containing different concentrations (3.15–150 µg/mL) of extracts or compounds, and control cells were treated with DMSO (0.5%) used to dissolve samples. After 72 h of treatment, 50 µL of XTT labeling reagent mixture solution was added in each well and the plate was incubated for 4 h. After incubation with the XTT reagent, the formazan formed is soluble in the medium and is directly proportional to the living cells. Then, cell viability was assessed by the measurement of the absorbance at 490 nm using a spectrophotometric microplate reader.

Each test was performed in triplicate. The IC50 (50% inhibitory concentration, that is, the concentration of extract or compound that inhibits 50% of the proliferation of cancer cells) value was calculated automatically from the sigmoidal dose–response nonlinear regression curve using GraphPad prism software.

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

3 Results and discussion

3.1 Structural elucidation of compounds

Chromatographic separation on silica gel of the CH2Cl2/MeOH (1:1) crude extract of leaves of C. fragrans F. Hoffm led to two new compounds (1 and 2) and five known compounds (3, 4, 5, 6, and 10), whereas the methanol crude extract from the stem bark yielded three known compounds (7, 8, and 9). The structures of the compounds were elucidated by spectral analysis using ESI-MS and 1D, 2D NMR data.

Compound 1 was isolated as a whitish powder and melted between 66.5 and 67.5°C. Its molecular formula, C27H46O5, implying five degrees of unsaturation, was deduced from its ESI-MS spectrum, which showed a pseudomolecular ion peak [M + 2Na]+ at m/z 496 in positive mode. Its IR spectrum showed broad absorption bands at 3,400 cm−1, indicating the presence of hydroxyl group at 1,735 cm−1 characteristic of a carbonyl of an ester moiety, and of aromatic ring between 1,450 and 1,600 cm−1, and C–O bonds (1,100 and 1,150 cm−1). The 1H NMR analysis revealed in up-field region the presence of a terminal methyl signal at δH 0.90 (3H, t, j = 6.9 Hz), with aliphatic methylene (–CH2–) signals ranging from δH 1.37 to 1.22 ppm, corresponding to an aliphatic chain. The spectrum also displayed resonances of α and β protons adjacent to the ester function of an aliphatic chain, respectively, at δH 2.33 (2H, t, j = 7.5 Hz) [12] and 1.64 (2H, dd, j = 7.5; 14.2 Hz), as well as the signal of an oxymethylene proton appearing at 4.10 (2H, t, j = 6.5 Hz). On the same spectrum, the signals of aromatics protons appeared as singlets at δH 6.45 (1H, s) and 6.31 ppm (1H, s) suggesting the presence of phenyl ring, one methoxy proton signal at δH 3.89 (3H, s), and a broad signal of free hydroxyl protons at δH 5.30 ppm as singlet. All the above information suggests an alkylphenyl skeleton. The 13C NMR broad-band showed 16 carbon signals, and together with HSQC and DEPT spectra, these signals were unambiguously assigned as: a carbonyl of ester at δC 174.0 (C-1), six tertiary and quaternary aromatic signals at δC 103.2, 108.5, 130.5, 133.1, 143.7, and 146.7, one oxymethylene carbon at δC 63.5, one methoxy carbon at δC 56.1, and one primary carbon at δC 14.1 corresponding to the terminal methyl of aliphatic chain. The signals of carbon atoms of the aliphatic chain at α and β positions to the carbonyl of the ester function appear at δC 34.4 and 25.0 respectively, and methylene carbon signals ranging from δC 29.2 to 29.7 correspond to a long aliphatic chain. In addition, two methylene carbon signals at δC 32.1 and 30.3 were attributed to the two methylenes between the phenyl group and the ester function. The two signals at δC 143.7 and 146.7 indicate that two of the oxygenated quaternary carbons are in ortho position. The 1H–1H COSY experiment shows correlations between the oxymethylene proton at δH 4.10 and the methylene proton at δH 1.93, which in turn correlates with another methylene proton at δH 2.59. These correlations suggest a propane chain substituted on position C-1ʹ and C-3ʹ enabling the assignment of chemical shifts at 4.10 to H-1ʹ, 1.93 to H-2ʹ, and 2.59 to H-3ʹ. The spectrum also shows correlations between the α and β protons to a carbonyl (ester) respectively at 2.31 (H-2) and 1.63 (H-3). The proton in β correlates in turn with the proton at δH 1.33 (H-4). The heteronuclear multiple bond correlation (HMBC) experiment shows correlations between the proton at 4.10 (H-1ʹ) and carbons at δC 32.0 (C-3ʹ), 30.5 (C-2ʹ) and a carbonyl signal at 173.9 (C-1). The spectrum also displays correlation between the proton at δH 1.93 (H-2ʹ) and carbons at δC 31.6 (C-3ʹ), 63.3 (C-1ʹ) as well as with an aromatic carbon signal at 133.2 (C-1″). Cross-peak correlations were also observed between the proton at δH 2.59 (H-3ʹ) and aromatic carbons at 108.3 (C-6″), 103.1 (C-2″), and 133.2 (C-1″) as well as carbons at δC 30.2 (C-2ʹ), 63.4 (C-1ʹ). Proton H-3 is the only proton that has several correlations with carbons from phenyl ring, indicating that C-3 is directly attached to the phenyl ring on C-1″ position. This result suggests that the aliphatic chain, which is a fatty ester, is located on C-1ʹ position of the propyl chain. In addition, the HMBC spectrum shows correlations of an aromatic proton at δH 6.45 (C-2″) with carbons at δC 31.9 (C-3ʹ), 108.6 (C-6″), 130.2 (C-4″), and 143 (C-3″). The aromatic proton at δH 6.30 (H-6″) correlates with different carbons at δC 31.9 (C-3ʹ), 103.2 (C-2″), 130.3 (C-4″), and 146.7 (C-5″). Proton of the methoxy group (δH 3.89) correlates with the carbon at δC 146.7, indicating that the methoxy group is attached on C-5″ position of the aromatic ring. Important HMBC correlations were also observed between the proton at δH 2.31 (H-2) from the long chain and carbons at δC 29.02 (C-4), 25.05 (C-3), and the carbonyl function at δC 173.98 (C-1). The length of the aliphatic chain was determined in conjunction with its 1H NMR spectrum and different fragmentation patterns observed on its mass spectrum. Characteristic fragments appeared at m/z 311, 253, and 181 (Figure S1). All these spectral data and some information reported in literature enabled us to characterize compound 1 as 3ʹ-(3″,4″-dihydroxy-5-methoxyphenyl)propyl heptadecanoate to which the trivial name fragransinate has been given. To the best of our knowledge, this compound is isolated for the first time from natural sources.

Compound 2 was isolated as a white powder and melted between 239.1 and 240.1°C. Its HRESI-MS mass spectrum in positive mode shows the pseudomolecular ion peak at m/z 643.4149 [M + Na]+ (calculated for C36H60O8, 643.4288) corresponding to the molecular formula C36H60O8 accounting seven degrees of unsaturation. The IR spectrum exhibits absorption bands νmax at 3,400 cm−1, 1,700 cm−1, and 1,000–1,025 cm−1, which were respectively attributable to a hydroxyl group, a carbonyl group, and C–O bonds. The analysis of its 1H NMR spectrum in conjunction with HSQC spectrum shows in upfield region the signals of two protons as doublet at δH 0.35 (1H, d, j = 4.0 Hz) and δH 0.54 (1H, d, j = 4.0 Hz) corresponding respectively to proton H-19b and H-19a of a cyclopropane from a cycloartane-type triterpene [13]. The spectrum also revealed the presence of six methyl groups at δH 0.80, 0.86, 0.92, 1.00, 1.01, and 1.03, and two oxymethine proton signals appearing at δH 3.24 (1H, m) and 3.96 (1H, dd, j = 11.0; 4.7 Hz). The spectrum also displays signals of osidic proton indicating the presence of a sugar moiety. Signals of oxymethine protons of a sugar moiety appeared at δH 3.67 (1H, dd, j = 11.3; 5.3 Hz), 3.24 (1H, m), 3.02; 2.97 (1H, m), 2.89 (1H, m) as well as the anomeric proton at 4.14 (1H, d, j = 7.5 Hz). The larger coupling constant (j = 7.5 Hz) of the anomeric proton suggests the β-configuration of the sugar moiety. The 1H NMR spectrum of compound 2 was very similar to that of Combretin B [9], except the missing signal of an olefinic proton in 2. Combretin B has been previously isolated from the same plant. The sugar moiety was identified as xylose. The 13C NMR spectrum confirmed the absence of olefinic function compared with that of Combretin B. The spectrum shows signals of 36 carbons including three methyl group signals as singlet at δC 18.9 (C-18), 10.0 (C-29), and 14.3 (C-30); four methyl group signals as doublet at δC 18.6 (C-21), 25.7 (C-26), 25.0 (C-27), and 18.6 (C-31); two oxymethine signals at δC 82.4 (C-3) and 71.2 (C-15); one carbonyl function at δC 177.5 (C-28). The signals of sugar moiety appear at δC 73.4 (C-2ʹ), 76.3 (C-3ʹ), 69.4 (C-4ʹ), and 65.5 (C-5ʹ) together with the anomeric carbon at δC 104.0 attributable to C-1ʹ. The HMBC experiment shows important correlation between the anomeric proton at δH 4.14 and the carbon at δC 82.43 (C-3), indicating that the sugar moiety is attached to the aglycone moiety at the C-3 position. Other correlations were also observed between the proton at δH 1.03 (H-29) and carbons at δC 177.59 (C-28), 82.43 (C-3), and 53.54 (C-4), indicating that the carbonyl group is located on C-28 position. According to the great similarity observed between compound 2 and Combretin B, the structure of compound 2 has been proposed as 3-(β-d-xylopyranosyl)-15α-hydroxycycloartan-28-oic acid for which the trivial name Combretin C has been given. The compound is isolated for the first time as a new derivative combretin triterpene.

The known compounds were identified from their NMR spectroscopic data and comparisons made with those reported in the literature: combretin A (3) [9]; belamcanidin (4), cirsilineol (5), velutin (6) [14]; betulinic acid (7) [15], bellericagenin B (8) [16], a mixture of β-sitosterol (9a) and stigmasterol (9b) [17]; and a mixture of β-sitosterol-3-O-β-d-glucopyranoside (10a) and stigmasterol-3-O-β-d-glucopyranoside (10b) [18]. Compounds 7, 8, 10a, and 10b are reported for the first time from this plant species.

3.2 Antiproliferative activity

The antiproliferative activity of extracts and compounds 2, 3, 5, and 8 of C. fragrans F. Hoffm on U87 human GBM cells, C6 rat GBM cells, and PC-3 prostate cancer was evaluated by XTT test. From the results presented in Table 3, it is deduced that the MeOH crude extract of the stem bark of C. fragrans F. Hoffm was found to be more active on all tested cells than the CH2Cl2/MeOH (1:1) crude extract from the leaves. The MeOH extract powerfully inhibits the proliferation of U87, C6, and PC-3 cells after 72 h treatment compared to untreated control cells. The extract was most active on PC-3 prostate cancer cells (IC50 = 11.24 µg/mL) than C6 (IC50 = 12.17 µg/mL) and U87 (IC50 = 20.13 µg/mL) cancer cells. On the contrary, the CH2Cl2/MeOH extract from the leaves also showed important inhibition of C6 cells proliferation (IC50 = 14.19 µg/mL) and moderate cytotoxicity effect on U87 (IC50 = 31 µg/mL) and PC-3 (36.26 µg/mL) cells. The literature mentions that many species from the combretum genus, similar to the specie studied here, are known to possess antiproliferative activity [8].

Table 3

Inhibitory concentration values of extracts and some compounds that kill or inhibit 50% of cancer cells (IC50 in µg/mL for extracts, and µM for compounds)

Extracts and compoundsU87 MGC6PC-3
IC50 values
CH2Cl2/MeOH extract31 µg/mL14.19 µg/mL36.26 µg/mL
MeOH extract20.13 µg/mL12.17 µg/mL11.24 µg/mL
2>100 µM>100 µM>100 µM
329.30 µM58.93 µM22.57 µM
565.46 µM31.61 µM30.46 µM
8>100 µM>100 µM>100 µM

Among the tested compounds, combretin A (3) was the most active followed by compound cirsilineol (5), whereas combretin C (2) and bellericagenin B (8) were not active. Compound 3 exhibited very good inhibition on PC-3 cells proliferation (IC50 = 22.57 µM), as well as on U87 (IC50 = 29.30 µM) and C6 cells (58.93 µM) which is moderated. Compound 5 also showed important inhibition on PC-3 (IC50 = 30.46 µM) and C6 (IC50 = 31.61 µM) cells’ proliferation and weak effect on U87 cells growth (IC50 = 65.46 µM). Compounds 3 and 5 isolated from the leaves could be responsible for the antiproliferative activity obtained with the related extract.

Combretin A (3) and C (2) are cycloartane-type triterpenes. The second is different from the first just by the presence in its structure of a sugar moiety on carbon C-3 and by the absence of a double bond on C-24 and C-31 carbons. However, combretin A showed good activity on all tested cells, whereas combretin C was inactive. The loss of the activity in combretin C could be attributable to the presence in its structure of the sugar moiety and the lack of the double bonds which negatively influences its activity. Previous study concerning structure–activity relationship showed that sugar moiety in gensenoside decreases its anticancer potential, whereas its aglycone presents good anticancer activity [19]. This study could explain our obtained results. Cycloartane triterpene types are also known for their anticancer activity [20,21], and this corroborates with the result obtained with combretin A. This is the first time that Combretin A is evaluated for its antiproliferative activity and it could be a good candidate for developping an anticancer agent in a pharmaceutical areas.

Compound (5) or cirsilineol is a flavonoid from flavonone type. Its activity was moderated on C6 and PC-3 cells but weak on U87MG cells. Its antiproliferative activity has already been documented for the first time on a large panel of cancer cell lines [22], and the results are similar with those obtained here with PC-3 cells. Flavonoids are known to possess anticancer activity, and this activity correlates positively with the presence of methoxyl group, carbonyl on carbon C-4, and the double bond on carbon C-2 and C-3 of flavonoids [23].

Compound (8) or bellericagenin B is an oleanane-12-ene triterpene type polyhydroxylated and showed no activity on all tested cancer cells. It is known that hydroxyl group correlates negatively with the anticancer activity in flavonoids [23] and other compounds [24]. Thus, the number of hydroxyl groups in compound 8 could explain its inactivity. In addition, compound 8 could be an oleanolic acid derivative and is different from this later with four hydroxyl groups. However, it is known that oleanolic acid, which possesses one hydroxyl group, has very good anticancer activity [25,26].

Betulinic acid (7) and stigmasterol (9b) were isolated from the bark and are known for their anticancer activity on many types of cancers [27,28]. Thus, the higher antiproliferative activity observed with the MeOH crude extract of the stem bark could be attributable in part to the presence of compounds 7 and 9b. The results of the antiproliferative activity of both extracts and some compounds of C. fragrans support with scientific evidences the traditional use of this plant in the treatment of cancer.

4 Conclusion

The present work describes the isolation and antiproliferative activity of extracts and some isolated compounds from C. fragrans F. Hoffm on GBM and prostate cancer cells. Column chromatographic separation on silica gel of the CH2Cl2/MeOH crude extract from the leaves yielded two new compounds (1 and 2) and five known compounds (3, 4, 5, 6, and 10), whereas the MeOH crude extract from the stem bark led to three known compounds (7, 8, and 9). Compounds 7, 8, and 10 were detected for the first time from this species. The results of the antiproliferative activity against U87, C6, and PC-3 cancer cells showed that the methanol crude extract from the stem bark exhibits powerful antiproliferative effect on all tested cells than the CH2Cl2/MeOH extract from leaves. As well, compound 3 was found to be the most active tested compound with highest effect on PC-3 cancer cells. The antiproliferative activity of extracts and compounds from C. fragrans F. Hoffm against U87, C6, and PC-3 cancer cells is reported here for the first time. In the future, we plan to isolate compound 1 with the aim of obtaining more compounds and testing its antiproliferative activity. This work can also serve as a guide for further isolation of compounds from other parts of C. fragrans F. Hoffm and evaluation of their anticancer properties as well as their toxicity.

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Acknowledgments

The authors thank the “Agence Universitaire de la Francophonie” for the financial support of this study. The authors are also grateful to Annie-Claire Balandre from the University of Poitiers for her helpful technical assistance. The authors also thank the team of the Laboratory of NMR and molecular imaging, University of Mons (Belgium) and the Laboratory of NMR, University of Poitiers (France) for NMR analysis.

  1. Funding information: This work was funded by “Agence Universitaire de la Francophonie” (AUF) to support research team in central Africa and great lakes: BAGL-2015-36.

  2. Authors’ contribution: I. S. G. – writing, conceptualization, formal analysis, and methodology; C. C., R. S. T., A. D. T. A., P. S., and B. V. – conceptualization, formal analysis, methodology, and manuscript revision; S. L. and C. H. – conducted the NMR and ESI-MS experiments; A. H. N. K. – project promoter; E. T. and J.-M. M. – supervised the research.

  3. Competing interests: The authors declare that they have no competing interests that could influence the work reported in this paper.

  4. Data availability statement: All data generated or analyzed during this study are included in this published article and its supplementary information files.

References

[1] Sudipta R, Dilip G, Rabinarayan A, Rajiv R. Combretum (Combretaceae): biological activity and phytochemistry. Indo Am J Pharm Res. 2014;4:5266–99.Search in Google Scholar

[2] Gedson RML, Igor RPS, Marcelo RDCF, Neyres ZTJ, Heloina SF, José MBF, et al. Bioactivities of the genus combretum (Combretaceae): a review. Molecules. 2012;17:9142–206.10.3390/molecules17089142Search in Google Scholar

[3] Wickens GE. Combretaceae. In: Polhill RM (ed.). Flora of tropical east Africa. London: Crown Agents for Oversea Governments and Administrations; 1973.Search in Google Scholar

[4] Maregesi SM, Ngassapa OD, Pieters L, Vlietinck AJ. Ethnopharmacological survey of the Bunda district, Tanzania: plants used to treat infectious diseases. J Ethnopharmacol. 2007;113:457–70.10.1016/j.jep.2007.07.006Search in Google Scholar

[5] Maima AO, Thoithi GN, Ndwigah SN, Kamau FN, Kibwage IO. Phytosterols from the stem bark of Combretum fragrans F. Hoffm. East Cent Afr J Pharm Sci. 2008;2008(11):52–4.10.4314/ecajps.v11i2.44769Search in Google Scholar

[6] Mbiantcha M, Almas J, Dawe A, Faheem A, Sidra Z. Analgesic, anti-inflammatory and anticancer activities of combretin A and combretin B isolated from Combretum fragrans F. Hoffm (Combretaceae) leaves. Inflammopharm. 2017;26:1429–40.10.1007/s10787-017-0421-5Search in Google Scholar

[7] Maregesi SM, Pieters L, Ngassapa OD, Apers S, Vingerhoets R, Cos P, et al. Screening of some Tanzanian medicinal plants from Bunda district for antibacterial, antifungal and antiviral activities. J Ethnopharmacol. 2008;119:58–66.10.1016/j.jep.2008.05.033Search in Google Scholar

[8] Fyhrquist P, Mwasumbi L, Vuorela P, Vuorela H, Hiltunen R, Murphy C, et al. Preliminary antiproliferative effects of some species of Terminalia, combretum and pteleopsis collected in Tanzania on some human cancer cell lines. Fitoterapia. 2006;77:358–66.10.1016/j.fitote.2006.05.017Search in Google Scholar

[9] Dawe A, Kapche GDWF, Bankeu JJK, Fawai Y, Ali MS, Ngadjui BT. Combretin A and B, new cycloartane-type triterpenes from Combretum fragrans. Helv Chim Acta. 2016;99:617–20.10.1002/hlca.201600053Search in Google Scholar

[10] Chhabra SC, Uiso FC. A survey of the medicinal plants of eastern Tanzania for alkaloids, flavonoids, saponins and tannins. Fitoterapia. 1990;61:307–16.Search in Google Scholar

[11] Scudiero DA, Shoemaker RH, Paull KD, Monks A, Tierney S, Nofziger TH, et al. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res. 1988;48:4827–33.Search in Google Scholar

[12] Marcel SFLKJ, David WYL. Preparation of 1-phenyl alkyl esters of medium and long-chain fatty acids. Chem Phys Lipids. 1989;50:155–61.10.1016/0009-3084(89)90039-XSearch in Google Scholar

[13] Toume K, Nakazawa T, Ohtsuki T, Arai MA, Koyano T, Kowithayakorn T, et al. Cycloartane triterpenes isolated from combretum quadrangulare in a screening program for death-receptor expression enhancing activity. J Nat Prod. 2011;74:249–55.10.1021/np100784tSearch in Google Scholar PubMed

[14] Dawé A, Mbiantcha M, Yakai F, Jabeen A, Shaiq MA, Lateef M, et al. Flavonoids and triterpenes from Combretum fragrans with anti-inflammatory, antioxidant and antidiabetic potential. Z Naturforsch. 2018;73:211–9.10.1515/znc-2017-0166Search in Google Scholar PubMed

[15] Ogunmoye A, Oladosu I, Onocha P, Choudhary I. Isolation of betulinic acid from the stem bark and root of Uapaca guineensis. J Res Rev Sci. 2017;91–6.10.36108/jrrslasu/7102/40(0121)Search in Google Scholar

[16] Mahato SB, Nandy AK, Kundu AP. Pentacyclic triterpenoid sapogenols and their glycosides from Terminalia bellerica. Tetrahedron. 1992;12:2483–94.10.1016/S0040-4020(01)88767-6Search in Google Scholar

[17] Luhata LP, Munkombwe NM. Isolation and characterisation of stigmasterol and β sitosterol from Odontonema strictum (Acanthaceae). J Innov Pharm Biol Sci. 2015;1:88–95.Search in Google Scholar

[18] Syafrinal Afrizal, Efdi M. Isolation and elucidation structure of stigmasterol glycoside from Nothopanax scutellarium Merr leaves. J Chem Pharm Res. 2015;7:763–5.Search in Google Scholar

[19] Qi LW, Wang CZ, Yuan CS. American ginseng: potential structure-function relationship in cancer chemoprevention. Biochem Pharmacol. 2010;80:947–54.10.1016/j.bcp.2010.06.023Search in Google Scholar PubMed

[20] Wang D, Ma Z. Cytotoxic activity of cycloartane triterpenoids from Sphaerophysa salsula. NPC. 2008;4:23–5.10.1177/1934578X0900400107Search in Google Scholar

[21] Shi QQ, Wang WH, Lu J, Li DS, Zhou L, Qiu MH. New cytotoxic cycloartane triterpenes from the aerial parts of Acteae heracleifolia (syn. Cimicifuga heracleifolia). Planta Med. 2018;85:154–9.10.1055/a-0733-7229Search in Google Scholar PubMed

[22] Sheng X, Sun Y, Yin Y, Chen T, Xu Q. Cirsilineol inhibits proliferation of cancer cells by inducing apoptosis via mitochondrial pathway. J Pharm Pharmacol. 2008;60:1523–9.10.1211/jpp.60.11.0014Search in Google Scholar

[23] Plochmann K, Korte G, Koutsilieri E, Richling E, Riederer P, Rethwilm A, et al. Structure-activity relationships of flavonoid-induced cytotoxicity on human leukemia cells. Arch Biochem Biophys. 2007;460:1–9.10.1016/j.abb.2007.02.003Search in Google Scholar PubMed

[24] Liew SK, Malagobadan S, Arshad NM, Nagoor NH. A review of the structure-activity relationship of natural and synthetic antimetastatic compounds. Biomolecules. 2020;10:138–66.10.3390/biom10010138Search in Google Scholar PubMed PubMed Central

[25] Yan SL, Huang CY, Wu ST, Yin MC. Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines. Toxicol Vitro. 2010;24:842–8.10.1016/j.tiv.2009.12.008Search in Google Scholar PubMed

[26] Zhu YY, Huang HY, Wu YL. Anticancer and apoptotic activities of oleanolic acid are mediated through cell cycle arrest and disruption of mitochondrial membrane potential in HepG2 human hepatocellular carcinoma cells. Mol Med Rep. 2015;12:5012–8.10.3892/mmr.2015.4033Search in Google Scholar PubMed PubMed Central

[27] Grothaus PG, Cragg GM, Newman DJ. Plant natural products in anticancer drug discovery. Curr Org Chem. 2010;14:1781–91.10.2174/138527210792927708Search in Google Scholar

[28] Zheng GQ. Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med. 1994;60:54–7.10.1055/s-2006-959408Search in Google Scholar PubMed

Received: 2020-06-26
Revised: 2020-08-06
Accepted: 2020-08-20
Published Online: 2020-12-31

© 2020 Isaac Silvère Gade et al., published by De Gruyter

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

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https://doi.org/10.1515/chem-2020-0167
Keywords for this article
Combretum fragrans F. Hoffm; fragransinate; combretin C; antiproliferative activity
Creative Commons
BY 4.0

Articles in the same Issue

  1. Regular Articles
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  3. Kinetic models of the extraction of vanillic acid from pumpkin seeds
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  14. Ducrosia ismaelis Asch. essential oil: chemical composition profile and anticancer, antimicrobial and antioxidant potential assessment
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  21. Assessment of methyl 2-({[(4,6-dimethoxypyrimidin-2-yl)carbamoyl] sulfamoyl}methyl)benzoate through biotic and abiotic degradation modes
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  31. N,N′-Bis[2-hydroxynaphthylidene]/[2-methoxybenzylidene]amino]oxamides and their divalent manganese complexes: Isolation, spectral characterization, morphology, antibacterial and cytotoxicity against leukemia cells
  32. Determination of the content of selected trace elements in Polish commercial fruit juices and health risk assessment
  33. Diorganotin(iv) benzyldithiocarbamate complexes: synthesis, characterization, and thermal and cytotoxicity study
  34. Keratin 17 is induced in prurigo nodularis lesions
  35. Anticancer, antioxidant, and acute toxicity studies of a Saudi polyherbal formulation, PHF5
  36. LaCoO3 perovskite-type catalysts in syngas conversion
  37. Comparative studies of two vegetal extracts from Stokesia laevis and Geranium pratense: polyphenol profile, cytotoxic effect and antiproliferative activity
  38. Fragmentation pattern of certain isatin–indole antiproliferative conjugates with application to identify their in vitro metabolic profiles in rat liver microsomes by liquid chromatography tandem mass spectrometry
  39. Investigation of polyphenol profile, antioxidant activity and hepatoprotective potential of Aconogonon alpinum (All.) Schur roots
  40. Lead discovery of a guanidinyl tryptophan derivative on amyloid cascade inhibition
  41. Physicochemical evaluation of the fruit pulp of Opuntia spp growing in the Mediterranean area under hard climate conditions
  42. Electronic structural properties of amino/hydroxyl functionalized imidazolium-based bromide ionic liquids
  43. New Schiff bases of 2-(quinolin-8-yloxy)acetohydrazide and their Cu(ii), and Zn(ii) metal complexes: their in vitro antimicrobial potentials and in silico physicochemical and pharmacokinetics properties
  44. Treatment of adhesions after Achilles tendon injury using focused ultrasound with targeted bFGF plasmid-loaded cationic microbubbles
  45. Synthesis of orotic acid derivatives and their effects on stem cell proliferation
  46. Chirality of β2-agonists. An overview of pharmacological activity, stereoselective analysis, and synthesis
  47. Fe3O4@urea/HITh-SO3H as an efficient and reusable catalyst for the solvent-free synthesis of 7-aryl-8H-benzo[h]indeno[1,2-b]quinoline-8-one and indeno[2′,1′:5,6]pyrido[2,3-d]pyrimidine derivatives
  48. Adsorption kinetic characteristics of molybdenum in yellow-brown soil in response to pH and phosphate
  49. Enhancement of thermal properties of bio-based microcapsules intended for textile applications
  50. Exploring the effect of khat (Catha edulis) chewing on the pharmacokinetics of the antiplatelet drug clopidogrel in rats using the newly developed LC-MS/MS technique
  51. A green strategy for obtaining anthraquinones from Rheum tanguticum by subcritical water
  52. Cadmium (Cd) chloride affects the nutrient uptake and Cd-resistant bacterium reduces the adsorption of Cd in muskmelon plants
  53. Removal of H2S by vermicompost biofilter and analysis on bacterial community
  54. Structural cytotoxicity relationship of 2-phenoxy(thiomethyl)pyridotriazolopyrimidines: Quantum chemical calculations and statistical analysis
  55. A self-breaking supramolecular plugging system as lost circulation material in oilfield
  56. Synthesis, characterization, and pharmacological evaluation of thiourea derivatives
  57. Application of drug–metal ion interaction principle in conductometric determination of imatinib, sorafenib, gefitinib and bosutinib
  58. Synthesis and characterization of a novel chitosan-grafted-polyorthoethylaniline biocomposite and utilization for dye removal from water
  59. Optimisation of urine sample preparation for shotgun proteomics
  60. DFT investigations on arylsulphonyl pyrazole derivatives as potential ligands of selected kinases
  61. Treatment of Parkinson’s disease using focused ultrasound with GDNF retrovirus-loaded microbubbles to open the blood–brain barrier
  62. New derivatives of a natural nordentatin
  63. Fluorescence biomarkers of malignant melanoma detectable in urine
  64. Study of the remediation effects of passivation materials on Pb-contaminated soil
  65. Saliva proteomic analysis reveals possible biomarkers of renal cell carcinoma
  66. Withania frutescens: Chemical characterization, analgesic, anti-inflammatory, and healing activities
  67. Design, synthesis and pharmacological profile of (−)-verbenone hydrazones
  68. Synthesis of magnesium carbonate hydrate from natural talc
  69. Stability-indicating HPLC-DAD assay for simultaneous quantification of hydrocortisone 21 acetate, dexamethasone, and fluocinolone acetonide in cosmetics
  70. A novel lactose biosensor based on electrochemically synthesized 3,4-ethylenedioxythiophene/thiophene (EDOT/Th) copolymer
  71. Citrullus colocynthis (L.) Schrad: Chemical characterization, scavenging and cytotoxic activities
  72. Development and validation of a high performance liquid chromatography/diode array detection method for estrogen determination: Application to residual analysis in meat products
  73. PCSK9 concentrations in different stages of subclinical atherosclerosis and their relationship with inflammation
  74. Development of trace analysis for alkyl methanesulfonates in the delgocitinib drug substance using GC-FID and liquid–liquid extraction with ionic liquid
  75. Electrochemical evaluation of the antioxidant capacity of natural compounds on glassy carbon electrode modified with guanine-, polythionine-, and nitrogen-doped graphene
  76. A Dy(iii)–organic framework as a fluorescent probe for highly selective detection of picric acid and treatment activity on human lung cancer cells
  77. A Zn(ii)–organic cage with semirigid ligand for solvent-free cyanosilylation and inhibitory effect on ovarian cancer cell migration and invasion ability via regulating mi-RNA16 expression
  78. Polyphenol content and antioxidant activities of Prunus padus L. and Prunus serotina L. leaves: Electrochemical and spectrophotometric approach and their antimicrobial properties
  79. The combined use of GC, PDSC and FT-IR techniques to characterize fat extracted from commercial complete dry pet food for adult cats
  80. MALDI-TOF MS profiling in the discovery and identification of salivary proteomic patterns of temporomandibular joint disorders
  81. Concentrations of dioxins, furans and dioxin-like PCBs in natural animal feed additives
  82. Structure and some physicochemical and functional properties of water treated under ammonia with low-temperature low-pressure glow plasma of low frequency
  83. Mesoscale nanoparticles encapsulated with emodin for targeting antifibrosis in animal models
  84. Amine-functionalized magnetic activated carbon as an adsorbent for preconcentration and determination of acidic drugs in environmental water samples using HPLC-DAD
  85. Antioxidant activity as a response to cadmium pollution in three durum wheat genotypes differing in salt-tolerance
  86. A promising naphthoquinone [8-hydroxy-2-(2-thienylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione] exerts anti-colorectal cancer activity through ferroptosis and inhibition of MAPK signaling pathway based on RNA sequencing
  87. Synthesis and efficacy of herbicidal ionic liquids with chlorsulfuron as the anion
  88. Effect of isovalent substitution on the crystal structure and properties of two-slab indates BaLa2−xSmxIn2O7
  89. Synthesis, spectral and thermo-kinetics explorations of Schiff-base derived metal complexes
  90. An improved reduction method for phase stability testing in the single-phase region
  91. Comparative analysis of chemical composition of some commercially important fishes with an emphasis on various Malaysian diets
  92. Development of a solventless stir bar sorptive extraction/thermal desorption large volume injection capillary gas chromatographic-mass spectrometric method for ultra-trace determination of pyrethroids pesticides in river and tap water samples
  93. A turbidity sensor development based on NL-PI observers: Experimental application to the control of a Sinaloa’s River Spirulina maxima cultivation
  94. Deep desulfurization of sintering flue gas in iron and steel works based on low-temperature oxidation
  95. Investigations of metallic elements and phenolics in Chinese medicinal plants
  96. Influence of site-classification approach on geochemical background values
  97. Effects of ageing on the surface characteristics and Cu(ii) adsorption behaviour of rice husk biochar in soil
  98. Adsorption and sugarcane-bagasse-derived activated carbon-based mitigation of 1-[2-(2-chloroethoxy)phenyl]sulfonyl-3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl) urea-contaminated soils
  99. Antimicrobial and antifungal activities of bifunctional cooper(ii) complexes with non-steroidal anti-inflammatory drugs, flufenamic, mefenamic and tolfenamic acids and 1,10-phenanthroline
  100. Application of selenium and silicon to alleviate short-term drought stress in French marigold (Tagetes patula L.) as a model plant species
  101. Screening and analysis of xanthine oxidase inhibitors in jute leaves and their protective effects against hydrogen peroxide-induced oxidative stress in cells
  102. Synthesis and physicochemical studies of a series of mixed-ligand transition metal complexes and their molecular docking investigations against Coronavirus main protease
  103. A study of in vitro metabolism and cytotoxicity of mephedrone and methoxetamine in human and pig liver models using GC/MS and LC/MS analyses
  104. A new phenyl alkyl ester and a new combretin triterpene derivative from Combretum fragrans F. Hoffm (Combretaceae) and antiproliferative activity
  105. Erratum
  106. Erratum to: A one-step incubation ELISA kit for rapid determination of dibutyl phthalate in water, beverage and liquor
  107. Review Articles
  108. Sinoporphyrin sodium, a novel sensitizer for photodynamic and sonodynamic therapy
  109. Natural products isolated from Casimiroa
  110. Plant description, phytochemical constituents and bioactivities of Syzygium genus: A review
  111. Evaluation of elastomeric heat shielding materials as insulators for solid propellant rocket motors: A short review
  112. Special Issue on Applied Biochemistry and Biotechnology 2019
  113. An overview of Monascus fermentation processes for monacolin K production
  114. Study on online soft sensor method of total sugar content in chlorotetracycline fermentation tank
  115. Studies on the Anti-Gouty Arthritis and Anti-hyperuricemia Properties of Astilbin in Animal Models
  116. Effects of organic fertilizer on water use, photosynthetic characteristics, and fruit quality of pear jujube in northern Shaanxi
  117. Characteristics of the root exudate release system of typical plants in plateau lakeside wetland under phosphorus stress conditions
  118. Characterization of soil water by the means of hydrogen and oxygen isotope ratio at dry-wet season under different soil layers in the dry-hot valley of Jinsha River
  119. Composition and diurnal variation of floral scent emission in Rosa rugosa Thunb. and Tulipa gesneriana L.
  120. Preparation of a novel ginkgolide B niosomal composite drug
  121. The degradation, biodegradability and toxicity evaluation of sulfamethazine antibiotics by gamma radiation
  122. Special issue on Monitoring, Risk Assessment and Sustainable Management for the Exposure to Environmental Toxins
  123. Insight into the cadmium and zinc binding potential of humic acids derived from composts by EEM spectra combined with PARAFAC analysis
  124. Source apportionment of soil contamination based on multivariate receptor and robust geostatistics in a typical rural–urban area, Wuhan city, middle China
  125. Special Issue on 13th JCC 2018
  126. The Role of H2C2O4 and Na2CO3 as Precipitating Agents on The Physichochemical Properties and Photocatalytic Activity of Bismuth Oxide
  127. Preparation of magnetite-silica–cetyltrimethylammonium for phenol removal based on adsolubilization
  128. Topical Issue on Agriculture
  129. Size-dependent growth kinetics of struvite crystals in wastewater with calcium ions
  130. The effect of silica-calcite sedimentary rock contained in the chicken broiler diet on the overall quality of chicken muscles
  131. Physicochemical properties of selected herbicidal products containing nicosulfuron as an active ingredient
  132. Lycopene in tomatoes and tomato products
  133. Fluorescence in the assessment of the share of a key component in the mixing of feed
  134. Sulfur application alleviates chromium stress in maize and wheat
  135. Effectiveness of removal of sulphur compounds from the air after 3 years of biofiltration with a mixture of compost soil, peat, coconut fibre and oak bark
  136. Special Issue on the 4th Green Chemistry 2018
  137. Study and fire test of banana fibre reinforced composites with flame retardance properties
  138. Special Issue on the International conference CosCI 2018
  139. Disintegration, In vitro Dissolution, and Drug Release Kinetics Profiles of k-Carrageenan-based Nutraceutical Hard-shell Capsules Containing Salicylamide
  140. Synthesis of amorphous aluminosilicate from impure Indonesian kaolin
  141. Special Issue on the International Conf on Science, Applied Science, Teaching and Education 2019
  142. Functionalization of Congo red dye as a light harvester on solar cell
  143. The effect of nitrite food preservatives added to se’i meat on the expression of wild-type p53 protein
  144. Biocompatibility and osteoconductivity of scaffold porous composite collagen–hydroxyapatite based coral for bone regeneration
  145. Special Issue on the Joint Science Congress of Materials and Polymers (ISCMP 2019)
  146. Effect of natural boron mineral use on the essential oil ratio and components of Musk Sage (Salvia sclarea L.)
  147. A theoretical and experimental study of the adsorptive removal of hexavalent chromium ions using graphene oxide as an adsorbent
  148. A study on the bacterial adhesion of Streptococcus mutans in various dental ceramics: In vitro study
  149. Corrosion study of copper in aqueous sulfuric acid solution in the presence of (2E,5E)-2,5-dibenzylidenecyclopentanone and (2E,5E)-bis[(4-dimethylamino)benzylidene]cyclopentanone: Experimental and theoretical study
  150. Special Issue on Chemistry Today for Tomorrow 2019
  151. Diabetes mellitus type 2: Exploratory data analysis based on clinical reading
  152. Multivariate analysis for the classification of copper–lead and copper–zinc glasses
  153. Special Issue on Advances in Chemistry and Polymers
  154. The spatial and temporal distribution of cationic and anionic radicals in early embryo implantation
  155. Special Issue on 3rd IC3PE 2020
  156. Magnetic iron oxide/clay nanocomposites for adsorption and catalytic oxidation in water treatment applications
  157. Special Issue on IC3PE 2018/2019 Conference
  158. Exergy analysis of conventional and hydrothermal liquefaction–esterification processes of microalgae for biodiesel production
  159. Advancing biodiesel production from microalgae Spirulina sp. by a simultaneous extraction–transesterification process using palm oil as a co-solvent of methanol
  160. Topical Issue on Applications of Mathematics in Chemistry
  161. Omega and the related counting polynomials of some chemical structures
  162. M-polynomial and topological indices of zigzag edge coronoid fused by starphene
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