Design and synthesis of potent antimalarial agents based on clotrimazole scaffold: exploring an innovative pharmacophore

J Med Chem. 2007 Feb 22;50(4):595-8. doi: 10.1021/jm061429p. Epub 2007 Jan 31.

Abstract

Identification of new molecular scaffolds structurally unrelated to known antimalarials may represent a valid strategy to overcome resistance of P. falciparum (Pf) to currently available drugs. We describe herein the investigation of a new polycyclic pharmacophore, related to clotrimazole, to develop innovative antimalarial agents. This study allowed us to discover compounds characterized by a high in vitro potency, particularly against Pf CQ-resistant strains selectively targeting free heme, which are easy to synthesize by low-cost synthetic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / pharmacology
  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology
  • Cell Line
  • Clotrimazole / analogs & derivatives*
  • Clotrimazole / chemical synthesis*
  • Clotrimazole / pharmacology
  • Drug Resistance
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • In Vitro Techniques
  • Models, Molecular
  • Plasmodium falciparum / drug effects
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Antimalarials
  • Heterocyclic Compounds, 4 or More Rings
  • Clotrimazole