Synthesis and Antifungal Potential of Some Novel Benzimidazole-1,3,4-Oxadiazole Compounds

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 1; p. 191
• Main Authors: Karaburun, Ahmet Çağrı, Kaya Çavuşoğlu, Betül, Acar Çevik, Ulviye, Osmaniye, Derya, Sağlık, Begüm Nurpelin, Levent, Serkan, Özkay, Yusuf, Atlı, Özlem, Koparal, Ali Savaş, Kaplancıklı, Zafer Asım
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.01.2019; MDPI
• Subjects: 1,3,4-oxadiazole; Amphotericin B; Antifungal activity; Antifungal agents; benzimidazole; Benzimidazoles; Biosynthesis; Carbon; cytotoxicity; Drug resistance; Drugs; Enzymes; Ergosterol; ergosterol biosynthesis; Evaluation; Fungal infections; Fungi; Fungicides; Ketoconazole; Lanosterol; molecular docking; Oxadiazoles; benzimidazole; molecular docking; antifungal activity; 1,3,4-oxadiazole; cytotoxicity; ergosterol biosynthesis
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24010191

Discovery of novel anticandidal agents with clarified mechanisms of action, could be a rationalist approach against diverse pathogenic fungal strains due to the rise of resistance to existing drugs. In support to this hypothesis, in this paper, a series of benzimidazole-oxadiazole compounds were synthesized and subjected to antifungal activity evaluation. In vitro activity assays indicated that some of the compounds exhibited moderate to potent antifungal activities against tested species when compared positive control amphotericin B and ketoconazole. The most active compounds and were evaluated in terms of inhibitory activity upon ergosterol biosynthesis by an LC-MS-MS method and it was determined that they inhibited ergosterol synthesis concentration dependently. Docking studies examining interactions between most active compounds and lanosterol 14-α-demethylase also supported the in vitro results.