Synthesis and antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines.
Navarrete-Vázquez G, Molina-Salinas GM, Duarte-Fajardo ZV, Vargas-Villarreal J, Estrada-Soto S, Estrada-Soto S, González-Salazar F, Hernández-Núñez E, Said-Fernández S.
4-(5-Substituted-1,3,4-oxadiazol-2-yl)pyridine derivatives 1-12 were synthesized and evaluated for their in vitro antimycobacterial activity. Some compounds showed an interesting activity against Mycobacterium tuberculosis H(37)Rv and five clinical isolates (drug-sensitive and -resistant strains). Compound 4 [4-(5-pentadecyl-1,3,4-oxadiazol-2-yl)pyridine] was 10 times more active than isoniazid, 20 times more active than streptomycin, and 28 times more potent than ethambutol against drug-resistant strain CIBIN 112. Compound 5 [4-(5-heptadecyl-1,3,4-oxadiazol-2-yl)pyridine] showed the same behavior as compound 4. Both of the above structures bear a high lipophilic chain bonded to the 5-position of the oxadiazole moiety. This fact implies that there exists a contribution of lipophilicity, which could facilitate the entrance of these molecules through lipid-enriched bacterial cell membrane.