Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides.

Abstract 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 (MIC 99  = 20, 10, and 20 μg/mL, respectively) and clinical MDR MS-115 resistant to five top antituberculosis drugs (МIC 99  = 50, 10, and 10 μg/mL, respectively).