Engelhardt Institute of Molecular Biology RAS, 32 Vavilova St., 119991, Moscow, Russia.
Engelhardt Institute of Molecular Biology RAS, 32 Vavilova St., 119991, Moscow, Russia.
Eur J Med Chem. 2021 Apr 5;215:113212. doi: 10.1016/j.ejmech.2021.113212. Epub 2021 Feb 1.
The emergence of drug-resistant strains of pathogenic microorganisms necessitates the creation of new drugs. In order to find new compounds that effectively inhibit the growth of pathogenic bacteria and fungi, we synthesized a set of N-derivatives of cytidine, 2'-deoxycytidine and 5-metyl-2'-deoxycytidine bearing extended N-alkyl and N-phenylalkyl groups. The derivatives demonstrate activity against a number of Gram-positive bacteria, including Mycobacterium smegmatis (MIC = 24-200 μM) and Staphylococcus aureus (MIC = 50-200 μM), comparable with the activities of some antibiotics in medical use. The most promising compound appeared to be N-dodecyl-5-metyl-2'-deoxycytidine 4h with activities of 24 and 48 μM against M. smegmatis and S. aureus, respectively, and high inhibitory activity of 0.5 mM against filamentous fungi that can, among other things, damage works of art, such as tempera painting. Noteworthy, some of other synthesized compounds are active against fungal growth with the inhibitory concentration in the range of 0.5-3 mM.
耐药菌株的出现使得新药物的研发成为必要。为了寻找能够有效抑制病原菌和真菌生长的新型化合物，我们合成了一系列带有长链 N-烷基和 N-苯烷基取代基的胞苷、2'-脱氧胞苷和 5-甲基-2'-脱氧胞苷的 N-衍生物。这些衍生物对多种革兰氏阳性菌具有活性，包括耻垢分枝杆菌（MIC = 24-200 μM）和金黄色葡萄球菌（MIC = 50-200 μM），与一些临床上使用的抗生素活性相当。最有前途的化合物似乎是 N-十二烷基-5-甲基-2'-脱氧胞苷 4h，对耻垢分枝杆菌和金黄色葡萄球菌的 MIC 值分别为 24 和 48 μM，对能够破坏艺术品（如蛋彩画）的丝状真菌具有高抑制活性，IC50 值为 0.5 mM。值得注意的是，其他一些合成化合物对真菌生长具有活性，抑制浓度在 0.5-3 mM 范围内。
