2. Academic Validation
  3. Synthesis and investigation of novel benzimidazole derivatives as antifungal agents

Synthesis and investigation of novel benzimidazole derivatives as antifungal agents

  • Bioorg Med Chem. 2016 Aug 15;24(16):3680-6. doi: 10.1016/j.bmc.2016.06.010.
Nishad Thamban Chandrika 1,  Sanjib K Shrestha 1,  Huy X Ngo 1,  Sylvie Garneau-Tsodikova 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536-0596, USA.
  • 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536-0596, USA. Electronic address: sylviegtsodikova@uky.edu.
PMID: 27301676 DOI: 10.1016/j.bmc.2016.06.010
Abstract

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 0.975μg/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.

Keywords

Aspergillus; Candida; Cytotoxicity; Hoechst 33258; Reactive oxygen species (ROS).

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