Synthesis and antimycobacterial activity of 4-(5-substituted-1,3,4-oxadiazol-2-yl)pyridines

• Published in: Bioorganic & medicinal chemistry Vol. 15; no. 16; pp. 5502 - 5508
• Main Authors: Navarrete-Vázquez, Gabriel, Molina-Salinas, Gloria Marı´a, Duarte-Fajardo, Zetel Vahi, Vargas-Villarreal, Javier, Estrada-Soto, Samuel, González-Salazar, Francisco, Hernández-Núñez, Emanuel, Said-Fernández, Salvador
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.08.2007; Elsevier Science
• Subjects: 1,3,4-Oxadiazoles; Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - toxicity; Biological and medical sciences; Cells, Cultured; Cercopithecus aethiops; Chemical Phenomena; Chemistry, Physical; Humans; Medical sciences; Molecular Structure; Multidrug-resistant strain; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - isolation & purification; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Oxadiazoles - toxicity; Pharmacology. Drug treatments; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - toxicity; Structure-Activity Relationship; Mycobacterium tuberculosis; 1,3,4-Oxadiazoles; Multidrug-resistant strain; Drug; Streptomycin; In vitro; Biological activity; Pyridine derivatives; Multidrug- resistant strain; Side chain; Mycobacteriales; Multiple resistance; Mycobacteriaceae; Oxadiazole derivatives; Bacteria; Ethambutol; Actinomycetes; Antituberculous agent; Antibacterial agent; Chemical synthesis; Clinical isolate; Isoniazid; Lipophilicity; Physicochemical properties
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.05.053

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 strain of Mycobacterium tuberculosis H 37Rv and five clinical isolates (drug-sensitive and -resistant strains). Compound 4 was 10, 20, and 28 times more active than isoniazid, streptomycin, and ethambutol against multidrug-resistant strain CIBIN 112. Compound 5 showed the same behavior as compound 4. Both structures bear a high lipophilic chain bonded to the 5-position of oxadiazole moiety. 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 37Rv 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.