Design, synthesis and antifungal activity of pterolactam-inspired amide Mannich bases

Fitoterapia. 2020 Jun:143:104581. doi: 10.1016/j.fitote.2020.104581. Epub 2020 Mar 29.

Abstract

Pterolactam (5-methoxypyrrolidin-2-one) is a heterocycle naturally occurring in plants. In an attempt to identify antifungal agents, a series of novel Mannich bases of amide derivated from Pterolactam have been designed, synthesized and their antifungal activities were evaluated on a panel of nine fungal strains and three non albicans candida yeasts species which have demonstrated reduced susceptibility to commonly used antifungal drugs. A third of the target compounds exhibited good to high antifungal activities on at least one strain with EC50 lower than the control antifungal agent. N,N'-aminals derivated from Pterolactam proved to be good candidates for the development of biosourced fungicides, with compound 3o being the most broader-spectrum agent, active against five strains and devoted of any cytotoxicity.

Keywords: Antifungal agents; Biological screening; N,N′-aminal; N,O-acetal; Pterolactam.

MeSH terms

  • Amides / chemical synthesis
  • Amides / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / pharmacology*
  • Fungi / drug effects
  • HEK293 Cells
  • Humans
  • Mannich Bases / chemical synthesis
  • Mannich Bases / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Amides
  • Antifungal Agents
  • Mannich Bases