Discovery of novel N 4 -alkylcytidines as promising antimicrobial agents

• Published in: European journal of medicinal chemistry 2021-04, Vol.215, p.113212
• Main Authors: Alexandrova, Liudmila A, Jasko, Maxim V, Negrya, Sergey D, Solyev, Pavel N, Shevchenko, Oleg V, Solodinin, Andrei P, Kolonitskaya, Daria P, Karpenko, Inna L, Efremenkova, Olga V, Glukhova, Alla A, Boykova, Yuliya V, Efimenko, Tatiana A, Kost, Natalya V, Avdanina, Darya A, Nuraeva, Gulgina K, Volkov, Ivan A, Kochetkov, Sergey N, Zhgun, Alexander A
• Format: Article
• Language: English
• ISSN: 1768-3254
• DOI: 10.1016/j.ejmech.2021.113212

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.