Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides.
Shmalenyuk ER, Chernousova LN, Karpenko IL, Kochetkov SN, Smirnova TG, Andreevskaya SN, Chizhov AO, Efremenkova OV, Alexandrova LA.
Two sets of pyrimidine nucleoside derivatives bearing extended alkyloxymethyl or alkyltriazolidomethyl substituents at position 5 of the nucleobase were synthesized and evaluated as potential antituberculosis agents. The impact of modifications at 3'- and 5'-positions of the carbohydrate moiety on the antimycobacterial activity and cytotoxicity was studied. The highest effect was shown for 5-dodecyloxymethyl-2'-deoxyuridine, 5-decyltriazolidomethyl-2'-deoxyuridine, and 5-dodecyltriazolidomethyl-2'-deoxycytidine. They effectively inhibited the growth of two Mycobacterium tuberculosis strains in vitro, laboratory H37Rv (MIC99=20, 10, and 20μg/mL, respectively) and clinical MDR MS-115 resistant to five top antituberculosis drugs (МIC99=50, 10, and 10μg/mL, respectively).