Synthesis and investigation of novel benzimidazole derivatives as antifungal agents

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• 作者：Nishad Thamban Chandrika^&dagger ; ; Sanjib K. Shrestha^&dagger ; ; Huy X. Ngo ; Sylvie Garneau-Tsodikova ; ^{sylviegtsodikova@uky.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Aspergillus ; Candida ; Cytotoxicity ; Hoechst 33258 ; Reactive oxygen species (ROS)
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：24
• 期：16
• 页码：3680-3686
• 全文大小：1157 K

文摘

The rise and emergence of resistance to antifungal drugs by diverse pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce reactive oxygen species (ROS) in yeast cells. Many of our bisbenzimidazole compounds exhibited moderate to excellent antifungal activities against all tested fungal strains, with MIC values ranging from 15.6 to 0.975 μg/mL. The fungal activity profiles of our bisbenzimidazoles were found to be dependent on alkyl chain length. Our most potent compounds were found to display equal or superior antifungal activity when compared to the currently used agents amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole against many of the strains tested.