Synthesis and Antitubercular Activity of New 5-Alkynyl Derivatives of 2-Thiouridine

Abstract

New efficient mycobacterial inhibitors based on 5-substituted 2-thiouridine derivatives have been described. A series of new 5-alkynyl-substituted 2-thiouridines have been synthesized in good yields by the palladium-catalyzed Sonogashira cross-coupling of 5-iodo-2-thiopyrimidine base with terminal alkynes in DMF at room temperature. The presence of a sulfur atm at C2 of the pyrimidine ring has been shown not to affect the yield of the target compounds. The synthesized 2-thiouridine derivatives were evaluated for their antimyco­bacterial activity against Mycobacterium bovis and Mycobacterium tuberculosis at concentrations of 0.1 to 100 μg/mL using microplate Alamar Blue assay (MABA). The compounds showed high antimycobacterial activity against both tested strains. The MIC50 values for 2-thionucleosides 14–16 (0.28–0.75 μg/mL) were much superior to those of the reference drugs rifampicin, D-cycloserine, and isoniazid, which makes these compounds promising for further more detailed study.