Synthesis and antifungal evaluation of phenol-derived bis(indolyl)methanes combined with FLC against Candida albicans

Bioorg Med Chem Lett. 2022 Feb 15:58:128525. doi: 10.1016/j.bmcl.2022.128525. Epub 2022 Jan 5.

Abstract

With the widespread use of azole antifungals in the clinic, the drug resistance has been emerging continuously. In this work, we focus on boron trifluoride etherate catalyzed condensation of indole and salicylaldehydes to form bis(indolyl)methanes (BIMs) in high yields, and in vitro antifungal activity against Candida albicans were evaluated. The results showed that most phenol-derived BIMs combined with fluconazole (FLC) exhibited good antifungal activity against sensitive and drug-resistant C. albicans. Further mechanism study demonstrated that BI-10 combined with FLC could inhibit hyphal growth, result in ROS accumulation, and decrease mitochondrial membrane potential (MMP) as well as altering membrane permeability.

Keywords: Antifungal activity; BF(3)•Et(2)O catalyzed synthesis; Bis(indolyl)methanes; Mechanistic studies.

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*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Fungal / drug effects
  • Fluconazole / chemistry
  • Fluconazole / pharmacology*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Methane / chemistry
  • Methane / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Indoles
  • Phenols
  • indole
  • Fluconazole
  • Methane