Synthesis and antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines.
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.
Navarrete-Vázquez
Gabriel
G
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62210, Mexico. gabriel-navarrete@uaem.mx
Molina-Salinas
Gloria María
GM
Duarte-Fajardo
Zetel Vahi
ZV
Vargas-Villarreal
Javier
J
Estrada-Soto
Samuel
S
González-Salazar
Francisco
F
Hernández-Núñez
Emanuel
E
Said-Fernández
Salvador
S
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002522:Chlorocebus aethiops; D006801:Humans; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000302:isolation & purification; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000995:Antitubercular Agents; D010069:Oxadiazoles; D011725:Pyridines; C023666:pyridine