Novel hybrids of fluconazole and furanones: Design, synthesis and antifungal activity

• Published in: Bioorganic & medicinal chemistry letters 2011-08, Vol.21 (16), p.4873-4878
• Main Authors: Borate, Hanumant B., Sawargave, Sangmeshwer P., Chavan, Subhash P., Chandavarkar, Mohan A., Iyer, Ramki, Tawte, Amit, Rao, Deepali, Deore, Jaydeep V., Kudale, Ananada S., Mahajan, Pankaj S., Kangire, Gopinath S.
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal activity; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; antifungal properties; Biological and medical sciences; Candida - drug effects; Candida albicans; Candida glabrata; Candida neoformans; Candida tropicalis; Dose-Response Relationship, Drug; Drug Design; Drug development; Fluconazole; Fluconazole - chemistry; Fluconazole - pharmacology; fungi; Furanones; Furans - chemistry; Furans - pharmacology; Hybrids; Medical sciences; Microbial Sensitivity Tests; Molecular Structure; pharmacology; Pharmacology. Drug treatments; pharmacophores; Stereoisomerism; Structure-Activity Relationship; Structure-activity relationships
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.06.022

A number of fluconazole analogues containing furanones were designed, synthesized and tested for their potential as antifungal agents against various fungal strains. The compounds with general structure 7 were potent inhibitors of Candida albicans ATCC 24433, Candida glabrata ATCC 90030, Candida tropicalis ATCC 750 and Candida neoformans ATCC 34664. The structure–activity relationship for these compounds is discussed. During our efforts to develop new antifungal agents, a number of hybrid molecules containing furanones and fluconazole pharmacophores were designed and synthesized. The new chemical entities thus synthesized were tested for their potential as antifungal agents against various fungal strains and it was observed that the compounds with general structure 7 were potent inhibitors of Candida albicans ATCC 24433, Candida glabrata ATCC 90030, Candida tropicalis ATCC 750 and Candida neoformans ATCC 34664 while the fluconazole analogues 12 exhibited antifungal activity against Candida albicans ATCC 24433 and Candida glabrata ATCC 90030. The structure–activity relationship for these compounds is discussed. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures to obtain molecules suitable for development as antifungal drugs.