Design, synthesis and antifungal activity of novel triazole derivatives containing substituted 1,2,3-triazole-piperdine side chains

Eur J Med Chem. 2014 Jul 23:82:490-7. doi: 10.1016/j.ejmech.2014.05.079. Epub 2014 Jun 2.

Abstract

Due to increasing incidence of invasive fungal infections and severe drug resistance to triazole antifungal agents, a series of novel antifungal triazoles with substituted triazole-piperidine side chains were designed and synthesized. Most of the target compounds showed good inhibitory activity against a variety of clinically important fungal pathogens. In particular, compounds 8t and 8v were highly active against Candida albicans and Cryptococcus neoformans with MIC values in the range of 0.125 μg/mL to 0.0125 μg/mL. They represent promising leads for the development of new generation of triazole antifungal agents. Molecular docking studies revealed that the target compounds interacted with CACYP51 mainly through hydrophobic and Van der Waals interactions.

Keywords: Antifungal activities; Click reaction; Triazole derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Cryptococcus neoformans / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Antifungal Agents
  • Piperidines
  • Triazoles