1H-1,2,3-triazole tethered mono- and bis-ferrocenylchalcone-β-lactam conjugates: synthesis and antimalarial evaluation

Eur J Med Chem. 2014 Oct 30:86:113-21. doi: 10.1016/j.ejmech.2014.08.053. Epub 2014 Aug 16.

Abstract

A series of ferrocenylchalcone-β-lactam conjugates were synthesized and evaluated against 3D7 (CQ-Sensitive) and W2 (CQ-Resistant) strains of Plasmodium falciparum. The SAR studies revealed the dependence of activities at N-1 substituent of β-lactam ring with compounds being more potent on resistant strain. The compound 9f and 9l with N-cyclohexyl substituent proved to be the most potent and non-cytotoxic among the series exhibiting IC50 values of 2.36 and 2.43 μM respectively, against W2 strain of P. falciparum.

Keywords: 1H-1,2,3-triazoles; Click chemistry; Ferrcenylchalcone-β-lactam conjugates; Plasmodium falciparum; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Dose-Response Relationship, Drug
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Structure-Activity Relationship
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • beta-Lactams / chemistry
  • beta-Lactams / pharmacology*

Substances

  • Antimalarials
  • Triazoles
  • beta-Lactams