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Synthesis and antimicrobial properties of 5,5′-modified 2′,5′-dideoxyuridines

  • Sergey D. Negria , Inna L. Karpenko , Olga V. Efremenkova , Alexander O. Chizhov , Sergey N. Kochetkov and Liudmila A. Alexandrova EMAIL logo
Published/Copyright: September 25, 2015
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Heterocyclic Communications
From the journal Heterocyclic Communications Volume 21 Issue 5

Abstract

An effective method of synthesis of 5,5′-modified 2′,5′-dideoxyuridine derivatives is based on sequential 5′-iodination and azidation of 5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine followed by 1,3-dipolar cycloaddition of the intermediate azide with an olefin under the catalysis of Cu(I) resulting in 75–85% yield of 5′-[4-substituted (1,2,3-triazol-1-yl]-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridine. The compounds were shown to possess low cytotoxicity in Vero, A549 cells and Jurkat cell cultures and did not demonstrate noticeable antimicrobial activity.

Keywords: 1,3-dipolar cycloaddition; antimicrobial activity; cytotoxicity; nucleoside analogue; synthesis

Introduction

At the present time, tuberculosis (TB) is one of the most widespread and dangerous diseases. The progress in drug design for the treatment of TB is complicated due to the appearance of drug-resistant Mycobacterium tuberculosis strains: practically incurable extensively drug-resistant (XDR) strains and multidrug-resistant (MDR) strains, which are barely affected by standard chemotherapy regimens [1]. Nucleoside analogues play an important role in medicine as antiviral and anticancer agents [2], but only at the beginning of this century it was found that several groups of modified nucleosides exhibit considerable in vitro antituberculosis activity in experimental models [3–11]. In particular, 5-modified pyrimidine nucleosides with extended 1-alkynyl substituents effectively inhibit the mycobacterial growth. The structure-activity relationship studies (SAR) of the carbohydrate fragment demonstrated that nearly all 2′-deoxy-, 2′,3′-dideoxy-, 3′-fluoro-2′,3′-dideoxy-, and 2′-fluoro-2′,3′-dideoxy- and arabinouridines, as well as acyclic and carbocyclic uridine derivatives with bulky 1-alkynyl substituents including 5′-norcarbocyclic derivatives, show antimycobacterial properties to a certain extent [3, 6–11].

Recently we synthesized pyrimidine nucleoside derivatives bearing extended substituents at the fifth position of the pyrimidine base as exemplified by compound 1 in Scheme 1. These compounds showed high bacteriostatic activity in vitro against two M. tuberculosis strains, namely laboratory H37Rv (which is a virulent strain susceptible to all anti TB drugs) and clinical MDR MS-115 (resistant to five first line antituberculosis drugs) [12, 13]. We also found that derivatives of 2′,5′-dideoxy-5-dodecyloxymethyluridine with additional azido- or iodo- substituents in the fifth position of the carbohydrate moiety retain antimycobacterial activity. The goal of this work was to synthesize and to study biological properties of 5,5′-modified 2′,5′-dideoxyuridine derivatives bearing extended substituents.

Scheme 1 (i) I2, Ph3P, imidazole, dioxane, 70°C; (ii) NaN3, DMF, 50°C; (iii) HC≡CCH2OH, CuSO4·5H2O, sodium ascorbate, CH2Cl2, room temperature; (iv) HC≡CCO2Et, CuSO4·5H2O, sodium ascorbate, CH2Cl2, room temperature; (v) aqueous NH3/dioxane, room temperature; (vi) 0.5 m KOH/dioxane, room temperature.
Scheme 1

(i) I2, Ph3P, imidazole, dioxane, 70°C; (ii) NaN3, DMF, 50°C; (iii) HC≡CCH2OH, CuSO4·5H2O, sodium ascorbate, CH2Cl2, room temperature; (iv) HC≡CCO2Et, CuSO4·5H2O, sodium ascorbate, CH2Cl2, room temperature; (v) aqueous NH3/dioxane, room temperature; (vi) 0.5 m KOH/dioxane, room temperature.

Results and discussion

5-[4-(1-Decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine (1) with good antimycobacterial properties [12], served as the key starting material in this work. 5′-Iodo-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridine (2) was prepared by the treatment of nucleoside 1 with iodine in the presence of triphenylphosphine and imidazole by the Moffatt method [14] with a yield of 72%. Treatment of compound 2with sodium azide in dimethylformamide at 70°С for 4 h as reported in [14] resulted in 5′-azido derivative 3in 93% yield.

1,3-Dipolar cycloaddition reaction between 1-acetylenes and azides catalyzed by copper(I) salts is widely known in organic chemistry as ‘click chemistry’. The resulting 1,2,3-triazole derivatives are capable of enhancing the binding of the compounds to biological targets due to the formation of additional hydrogen bonds and dipole interactions [15]. In this work, the 1,3-dipolar cycloaddition of azide 3 with the proper olefins in a binary phase system of dichloromethane-water under the catalysis of Cu(I) obtained in situ [16] resulted in 75–85% yields of 5′-[4-substituted (1,2,3-triazol-1-yl]-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridines 4and 5. The treatment of nucleoside 5 with aqueous ammonia or potassium hydroxide gave the respective compounds 6and 7.

Cytotoxicity (CD50) of the synthesized compounds was estimated by using an МТТ assay [17]. Compounds were not cytotoxic at concentrations up to 150 μg/mL in Vero, and up to 75 μg/mL in A549 and Jurkat cell cultures. As shown by Kumar and coworkers, 5-alkynyl-2′-deoxyuridine derivatives with various modifications of the carbohydrate residue inhibit some Gram-positive bacteria at high concentrations (MIC100= 100 μg/mL) [7, 8, 10]. Previously, we demonstrated that only α-anomer of 5-dodecyloxymethyl-2′-deoxyuridine at a high concentration displayed antibiotic properties toward Gram-positive Leuconostoc mesenteroides B-4177 [12]. Compounds did not demonstrate noticeable antimicrobial activity against eight Gram-positive (including Mycobacterium smegmatis) and two Gram-negative bacteria and did not inhibit the growth of two fungi cultures and yeast (the details are given in the experimental part).

Conclusions

Sequential 5′-iodination and azidation of 5-[4(1-decyl)-1,2,3-triazol-1-yl]methyl-2′-deoxyuridine followed by 1,3-dipolar cycloaddition of the resultant azide with the proper olefins under the catalysis of Cu(I) resulted in the formation of 5′-[4-substituted (1,2,3-triazol-1-yl]-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridines in good yields. The obtained compounds show low cytotoxicity in Vero and A549 cells and Jurkat cell cultures and do not demonstrate noticeable antimicrobial activity. These results indicate that the introduction of a bulky group in the position 5′ of the nucleoside moiety causes the loss of antibacterial activity.

Experimental

Column chromatography was performed on silica gel 60 (0.040–0.063 mm, Merck, Germany). Thin layer chromatography (TLC) was performed on silica gel 60 F254 plates (Merck, Germany). Preparative TLC was performed on glass plates 20 x 20 x 2 mm pre-coated with silica gel 60 F254 (Merck, Germany). NMR spectra were registered in DMSO-d6 on an AMX III-400 spectrometer (Bruker, USA) with the working frequency of 400 MHz for 1H NMR and 100.6 MHz for 13C NMR (with the carbon–proton decoupling). The assignment of exchangeable protons (OH, NH) was confirmed by the addition of D2O. UV spectra were recorded in water on a UV-2401PC spectrophotometer (Shimadzu, Japan) in ethanol at pH 7.0. High resolution mass spectra were measured on Bruker micrOTOF II or maXis (Bruker, Germany) instruments using electrospray ionization [18] in a positive ion mode (interface capillary voltage of 4500 V). IR spectra were recorded on a Shimadzu IR-435 spectrophotometer (Japan) in mineral oil.

5′-Iodo-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridine (2)

To a solution of nucleoside 1(300 mg, 0.7 mmol), imidazole (95 mg, 1.4 mmol) and triphenylphosphine (733 mg, 2.8 mmol) in anhydrous dioxane (25 mL) a solution of iodine (711 mg, 2.8 mmol) in dioxane (15 mL) was added dropwise within an hour at room temperature. Then this mixture was treated with an aqueous solution of sodium sulfite (5 mL, 1 M) and concentrated under a reduced pressure. The residue was partitioned between ethyl acetate (10 mL) and water (5 mL), and the organic layer was washed with water (2 × 2 mL), dried over Na2SO4, and concentrated under a reduced pressure. The crude product was purified on a silica gel column (2 × 15 cm) eluting with chloroform/methanol (40:1, v/v) to give 3 as a light yellow solid: yield 270 mg (72%); UV: λmax 264.3 nm (ε 9780); 1H NMR: δ 0.83–0.86 (3H, m, J = 7 Hz ,(CH2)9CH3), 1.25–1.35 (14H, m, CH2CH2(CH2)7CH3), 1.53–1.60 (2H, m, CH2CH2(CH2)7CH3), 2.14–2.20 (1H, ddd, J = 4 Hz, 7 Hz and 14 Hz, H-2′-a), 2.26–2.32 (1H, m, H-2′-b) 2.54–2.58 (2H, t, J 7 Hz, CH2CH2(CH2)7CH3), 3.34–3.38 (1H, dd, J 6 Hz, J 10 Hz, H-5′-a), 3.46–3.50 (1H, dd, J 6 Hz, J 10 Hz, H-5′-b), 3.81–3.85 (1H, td, J = 3 Hz and 6 Hz, H-4′), 4.16–4.21 (1H, m, H-3′), 5.16 (2H, s, 5-CH2), 5.49–5.50 (1H, d, J = 4 Hz, OH-3′), 6.18–6.22 (1H, t, J = 7 Hz, H-1′), 7.75 (1H, s, H-6), 7.89 (1H, s, 5-CH (5-triazolyl)), 11.58 (1H, s, NH); 13C NMR: δ 7.45 (C-5′), 13.9 ((CH2)9CH3), 22.0–31.2 ((CH2)9), 38.3 (C-2′), 45.6 (5-CH2), 72.9 (C-3′), 84.5 (C-4′), 85.6 (C-1′), 108.4 (C-5), 121.7 (CH (5-triazolyl)), 140.6 (C-6), 146.8 (C-C10H21), 150.1 (C-2), 162.4 (C-4). HRMS (ESI). Calcd for C22H35IN5O4 ([M+H]+): m/z 560.1718. Found: m/z 560.1728. Calcd for C22H34IN5O4Na ([M+Na]+): m/z 582.1536. Found: m/z 582.1548.

5′-Azido-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridine (3)

A solution of nucleoside 2 (200 mg, 0.36 mmol) and sodium azide (96 mg, 1.5 mmol) in DMF (20 mL) was stirred for 4 h at 70°С. Then the mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate (10 mL) and water (5 mL). The organic layer was washed with water (2 × 2 mL), dried over Na2SO4, and concentrated under reduced pressure. The crude product was purified on a silica gel column (2 × 15 cm) using chloroform/methanol (40:1, v/v) as an eluent to give 3; yield 160 mg (93%); UV: λmax261.8 nm (ε 9780); IR: 2112 cm-1 (azide); 1H NMR: δ 0.83–0.87 (3H, t, J = 7 Hz, (CH2)9CH3), 1.23–1.35 (14H, m, CH2CH2(CH2)7CH3), 1.53–1.57 (2H, m, CH2CH2(CH2)7CH3), 2.13–2.20 (1H, ddd, J = 4 Hz, 7 Hz and 14 Hz, H-2′-a), 2.26–2.32 (1H, dt, J = 7 Hz and 14 Hz, H-2′-b), 2.54–2.58 (2H, t, J = 7 Hz, CH2CH2(CH2)7CH3), 3.54–3.56 (2H, m, H-5′), 3.84–3.90 (1H, m, H-4′), 4.18–4.22 (1H, m, H-3′), 5.16 (2H, s, 5-CH2), 6.16–6.20 (1H, t, J = 7 Hz, H-1′), 7.73 (1H, s, H-6), 7.90 (1H, s, 5-CH (5-triazolyl)), 11.52 (1H, s, NH); 13C NMR: δ. 13.8 ((CH2)9CH3), 22.0–31.2 (-(CH2)9), 38.4 (C-2′), 45.7 (5-CH2), 51.6 (C-5′), 70.5 (C-3′), 84.4 (C-1′), 84.6 (C-4′), 108.4 (C-5), 121.5 (CH (5-triazolyl)), 140.5 (C-6), 146.7 (C-C10H21), 150.6 (C-2), 163.0 (C-4). HRMS (ESI). Calcd for C22H35N8O4 ([M+H]+): m/z 475.2779. Found: m/z 475.2776. Calcd for C22H34N8O4Na ([M+Na]+): m/z 497.2425. Found: m/z 497.2595. Calcd for C22H34N8O4K ([M+K]+): m/z 513.2334. Found: m/z 513.2335.

5′-[4-Hydroxymethyl-1,2,3-triazol-1-yl]-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridine (4)

To a solution of 3 (60 mg, 0.13 mmol) in dichloromethane (10 mL) propargyl alcohol (17 mg, 0.3 mmol), an aqueous solution (1.5 mL) of CuSO4 (25 mg, 0.2 mmol) and an aqueous solution (1.5 mL) of sodium ascorbate (39.6 mg, 0.2 mmol) were added and the mixture was stirred for 24 h at room temperature. The crude product was purified on a silica gel column (2 × 15 cm) using chloroform/methanol (9:1, v/v) as an eluent to give 4 (63 mg, 92%); UV: λmax 262.4 nm (ε 9780); 1H NMR: δ 0.83–0.87 (3H, t, J = 7 Hz, (CH2)9CH3), 1.20–1.35 (14H, m, CH2CH2(CH2)7CH3), 1.54–1.58 (2H, m, CH2CH2(CH2)7CH3), 2.15–2.26 (2H, m, H-2′), 2.55–2.59 (2H, t, J = 7 Hz, CH2CH2(CH2)7CH3), 4.09–4.13 (1H, dt, J = 4 Hz and 8 Hz, H-4′), 4.27–4.31 (1H, dd, J = 4 Hz and 9 Hz, H-3′), 4.51–4.52 (2H, d, J = 6 Hz, 5′-(triazolyl)-CH2OH), 4.56–4.62 (1H, dd, J = 8 Hz and 14 Hz, H-5′-a), 4.69–4.74 (1H, dd, J = 4 Hz and 14 Hz, H-5′-b), 5.15–5.17 (1H, t, J = 6 Hz, 5′-(triazolyl)-CH2OH), 5.17 (2H, s, 5-CH2), 5.50–5.51 (1H, d, J = 4 Hz, 3′-OH), 6.15–6.19 (1H, t, J = 7 Hz, H-1′), 7.78 (1H, s, H-6), 7.91 (1H, s, 5-CH (5-triazolyl)), 7.96 (1H, s, 5-CH (5′-triazolyl)), 11.54 (1H, s, NH); 13C NMR: δ. 13.9 ((CH2)9CH3), 22.0–31.2 ((CH2)9), 39.1 (C-2′), 45.6 (5-CH2), 51.2 (C-5′), 54.9 (CH2OH (5′-triazolyl)), 70.8 (C-3′), 84.5 (C-1′), 84.8 (C-4′), 108.3 (C-5), 121.7 (CH (5-triazolyl)), 123.4 (CH (5′-triazolyl)), 141.0 (C-6), 146.7 (-C-C10H21), 148.0 (C-CH2OH), 150.1 (C-2), 162.4 (C-4). HRMS (ESI): Calcd for C25H39N8O5 ([M+H]+): m/z 530.2965. Found: m/z 530.2954. Calcd for C25H38N8O5Na ([M+Na]+): m/z 553.2864. Found: m/z 553.2857.

5′-[4-Ethoxycarbonyl-1,2,3-triazol-1-yl]-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridine (5)

A solution of 3 (80 mg, 0.17 mmol) in dichloromethane (10 mL) was treated with propargyl alcohol (17 mg, 0.3 mmol), an aqueous solution (1.5 mL) of sodium ascorbate (79 mg, 0.4 mmol) and an aqueous solution (1.5 mL) of CuSO4 (50 mg, 0.4 mmol) and the mixture was stirred for 24 h at room temperature. The crude product was purified on a silica gel column (2 × 15 cm) using chloroform/methanol (9:1, v/v) as an eluent to give 5 (92 mg, 95%); UV: λmax 262.2 nm (ε 9780); 1H NMR: δ 0.83–0.86 (3H, t, J = 7 Hz, (CH2)9CH3), 1.23–1.28 (14H, m, CH2CH2(CH2)7CH3), 1.27–1.30 (3H, t, J = 7 Hz, (COOCH2)CH3), 1.53–1.57 (2H, m, CH2CH2(CH2)7CH3), 2.17–2.32 (2H, m, H-2′), 2.54–2.56 (2H, t, J = 8 Hz, CH2CH2(CH2)7CH3), 4.12–4.16 (1H, m, H-4′), 4.26–4.31 (3H, m, H-3′, CH2(Et)), 4.64–4.70 (1H, dd, J = 8 Hz and 14 Hz, H-5′-a), 4.76–4.81 (1H, dd, J = 5 Hz and 14 Hz, H-5′-b), 5.13 (2H, s, 5-CH2), 5.50–5.51 (1H, d, J = 5 Hz, OH-3′), 6.13–6.17 (1H, t, J = 7 Hz, H-1′), 7.76 (1H, s, H-6), 7.86 (1H, s, 5-CH (5-triazolyl)), 8.72 (1H, s, 5-CH (5′-triazolyl)), 11.58 (1H, s, NH); 13C NMR: δ. 13.8 ((CH2)9CH3), 14.1 ((COOCH2)CH3), 22.0–31.2 ((CH2)9), 39.1 (C-2′), 45.6 (5-CH2), 51.4 (C-5′), 60.5 ((COO)CH2CH3), 70.6 (C-3′), 83.9 (C-1′), 84.9 (C-4′), 108.2 (C-5), 121.5 (CH (5-triazolyl)), 129.5 (CH (5′-triazolyl)), 138.9 (C-COOEt), 141.1 (C-6), 146.7 (C-C10H21), 150.0 (C-2), 160.1 (-COOEt), 162.3 (C-4). HRMS (ESI). Calcd for C27H41N8O6([M+H]+): m/z 572.3071. Found: m/z 572.3067. Calcd for C27H40N8O6Na ([M+Na]+): m/z 595.2968. Found: m/z 595.2963.

5′-[4-Aminocarbonyl-1,2,3-triazol-1-yl]-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridine (6)

A solution of 5(40 mg, 0.07 mmol) in dioxane (2 mL) was mixed with 32% aqueous ammonia (2 mL) and the mixture was stirred for 24 h at 20°С. The crude product was purified by preparative thin-layer chromatography on silica gel using chloroform/methanol (4:1, v/v) as an eluent to give 6 (30 mg, 79%); UV: λmax 261.6 nm (ε 9780); 1H NMR: δ 0.82–0.86 (3H, m, J = 7 Hz, (CH2)9CH3), 1.14–1.22 (14H, m, CH2CH2(CH2)7CH3), 1.53–1.56 (2H, m, CH2CH2(CH2)7CH3), 2.16–2.22 (1H, dd, J = 7 Hz and 13 Hz, H-2′-a), 2.24–2.29 (1H, dd, J = 7 Hz and 13 Hz, H-2′-b), 2.54–2.58 (2H, t, J = 8 Hz, CH2CH2(CH2)7CH3), 4.11–4.14 (1H, m, H-4′), 4.26–4.30 (1H, m, H-3′), 4.62–4.67 (1H, dd, J = 8 Hz and 14 Hz, H-5′-a), 4.75–4.79 (1H, dd, J = 5 Hz and 14 Hz, H-5′-b)), 5.15–5.16 (2H, d, J = 5 Hz, 5-CH2), 5.53–5.54 (1H, d, J = 4 Hz, OH-3′), 6.14–6.17 (1H, t, J = 7 Hz, H-1′), 7.45 (1H, s, NH2(a)), 7.77 (1H, s, H-6), 7.81 (1H, s, NH2(b)), 7.90 (1H, s, 5-CH (5-triazolyl)), 8.50 (1H, s, 5-CH (5′-triazolyl)), 11.54 (1H, s, NH). HRMS (ESI). Calcd for C25H38N9O5 ([M+H]+): m/z 544.2983. Found: m/z 544.2990. Calcd for C25H37N9O5Na ([M+Na]+): m/z 566.2808. Found: m/z 566.2810.

5′-[4-Carboxy-1,2,3-triazol-1-yl]-5-[4-(1-decyl)-1,2,3-triazol-1-yl]methyl-2′,5′-dideoxyuridine (7)

A solution of 5(21 mg, 0.037 mmol) in dioxane (2 mL) was mixed with 0.5 M aqueous solution of KOH (0.5 mL) and the mixture was stirred for an hour at 20°С. The crude product was purified by preparative thin-layer chromatography on silica gel using dioxane/ammonia (4:1, v/v) as an eluent to give 7 (14 mg, 70%); UV: λmax 264.4 nm (ε 9780); 1H NMR: δ 0.83–0.86 (3H, t, J = 7 Hz, (CH2)9CH3), 1.20–1.35 (14H, m, CH2CH2(CH2)7CH3), 1.53–1.57 (2H, t, J = 7 Hz, CH2CH2(CH2)7CH3), 2.15–2.27 (2H, m, H-2′), 2.54–2.58 (2H, t, J 7 Hz, CH2CH2(CH2)7CH3), 4.10–4.14 (1H, m, H-4′), 4.27–4.30 (1H, m, H-3′), 4.59–4.64 (1H, dd, J = 7 Hz and 14 Hz, H-5′-a), 4.71–4.76 (1H, dd, J = 5 Hz and 14 Hz, H-5′-b), 5.16–5.17 (2H, d, J = 3 Hz, 5-CH2), 6.14–6.17 (1H, t, J = 7 Hz, H-1′), 7.69 (1H, s, H-6), 7.79 (1H, s, 5-CH (5-triazolyl)), 7.87 (1H, s, COOH), 8.38 (1H, s, 5-CH (5′-triazolyl)), 11.28 (1H, s, NH); 13C NMR: δ 13.9 ((CH2)9CH3), 22.0–31.2 ((CH2)9), 38.1 (C-2′), 45.6 (5-CH2), 51.2 (C-5′), 70.7 (C-3′), 84.2 (C-1′), 84.8 (C-4′), 108.2 (C-5), 121.6 (CH (5-triazolyl)), 128.0 (C-COOH), 130.2 (CH (5′-triazolyl)), 141.0 (C-6), 146.7 (C-C10H21), 150.1 (C-2), 160.1 (COOH), 162.3 (C-4). HRMS (ESI). Calcd for C52H36N8O6Na ([M+Na]+): m/z 567.2654. Found: m/z 567.2650.

Cytotoxicity

Vero cells (green monkey kidney epithelial cells, ATCC No CRL-1586), A549 cells (lung carcinoma cell line, ATCC No CCL-185), Jurkat cells (T lymphocyte cell line, ATCC No CRL-2676) were provided by Laboratory of cell cultures, Ivanovsky Institute of virology RAMS (Moscow) and Engelhardt Institute of molecular biology RAS (Moscow).

Cytotoxicity (CD50) was estimated by МТТ-assay [11] in the presence of tested compounds at the concentrations from 0 to 200 μg/mL after 72 h of incubation with uninfected cells and calculated as compound concentration, at which 50% of cells died.

The test-organisms chosen to determine the antibiotic activity

The following test-organisms were used: Gram-positive bacteria – Bacillus subtilis АТСС 6633, Bacillus pumilis NCTC 8241, Bacillus mycoides 537, Micrococcus luteus NCTC 8340, Leuconostoc mesenteroides VKPM B-4177 (the strains resistant to glycopeptide antibiotics of vancomycin group), Staphylococcus aureus FDA 209P (methicillin-susceptible strains, MSSA), Staphylococcus aureus INA00761 (methicillin-resistant strain, MRSA), Mycobacterium smegmatis mc2155; Gram-negative bacteria – Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae INA 01117; filamentous fungus – Aspergillus niger INA00760, yeast – Saccharomyces cerevisiae RIA259 [19].

Corresponding author: Liudmila A. Alexandrova, Engelhardt Institute of Molecular Biology RAS, Vavilov str. 32, Moscow 119991, Russia, e-mail:

Acknowledgments

This work was supported by the Fundamental Research Program of the Presidium of the Russian Academy of Sciences ‘Molecular and Cell Biology’ and the Russian Foundation for Basic Research (Grants no 14-04-00755 and 15-04-05116).

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Supplemental Material:

The online version of this article (DOI: 10.1515/hc-2015-0166) offers supplementary material, available to authorized users.

Received: 2015-8-6
Accepted: 2015-8-27
Published Online: 2015-9-25
Published in Print: 2015-10-1

©2015 by De Gruyter

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  1. Frontmatter
  2. Guest Editorial
  3. Dedication to Kyoichi A. Watanabe
  4. Review
  5. From ribavirin to NAD analogues and back to ribavirin in search for anticancer agents
  6. Preliminary Communications
  7. 5′-Norcarbocyclic analogues of furano[2,3-d]pyrimidine nucleosides
  8. Fluorescent 1,2,3-triazole derivative of 3′-deoxy-3-azidothymidine: synthesis and absorption/emission spectra
  9. Research Articles
  10. Synthesis and characterization of N-glucosylated dithiadiazepine derivatives through carbon-sulfur bond formation
  11. Synthesis of 8-alkoxy-1,3-dimethyl-2, 6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides as analgesic and anti-inflammatory agents
  12. 13C NMR spectroscopy of heterocycles: 3,5-diaryl-4-bromoisoxazoles
  13. Synthesis and anti-proliferative activity of pyridine O-galactosides and 4-fluorobenzoyl analogues
  14. Optimized synthesis of 3′-O-aminothymidine and evaluation of its oxime derivative as an anti-HIV agent
  15. Synthesis and antimicrobial properties of 5,5′-modified 2′,5′-dideoxyuridines
  16. Acyclic analogs of nucleosides based on tris(hydroxymethyl)phosphine oxide: synthesis and incorporation into short DNA oligomers
  17. Synthesis and antiviral evaluation of 2′,3′-dideoxy-2′,3′-difluoro-D-arabinofuranosyl 2,6-disubstituted purine nucleosides
https://doi.org/10.1515/hc-2015-0166
Keywords for this article
1,3-dipolar cycloaddition; antimicrobial activity; cytotoxicity; nucleoside analogue; synthesis
Creative Commons
BY-NC-ND 3.0

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Dedication to Kyoichi A. Watanabe
  4. Review
  5. From ribavirin to NAD analogues and back to ribavirin in search for anticancer agents
  6. Preliminary Communications
  7. 5′-Norcarbocyclic analogues of furano[2,3-d]pyrimidine nucleosides
  8. Fluorescent 1,2,3-triazole derivative of 3′-deoxy-3-azidothymidine: synthesis and absorption/emission spectra
  9. Research Articles
  10. Synthesis and characterization of N-glucosylated dithiadiazepine derivatives through carbon-sulfur bond formation
  11. Synthesis of 8-alkoxy-1,3-dimethyl-2, 6-dioxopurin-7-yl-substituted acetohydrazides and butanehydrazides as analgesic and anti-inflammatory agents
  12. 13C NMR spectroscopy of heterocycles: 3,5-diaryl-4-bromoisoxazoles
  13. Synthesis and anti-proliferative activity of pyridine O-galactosides and 4-fluorobenzoyl analogues
  14. Optimized synthesis of 3′-O-aminothymidine and evaluation of its oxime derivative as an anti-HIV agent
  15. Synthesis and antimicrobial properties of 5,5′-modified 2′,5′-dideoxyuridines
  16. Acyclic analogs of nucleosides based on tris(hydroxymethyl)phosphine oxide: synthesis and incorporation into short DNA oligomers
  17. Synthesis and antiviral evaluation of 2′,3′-dideoxy-2′,3′-difluoro-D-arabinofuranosyl 2,6-disubstituted purine nucleosides
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