Transition Metal Complexes as Antimalarial Agents: A Review

ChemMedChem. 2023 Oct 4;18(19):e202300326. doi: 10.1002/cmdc.202300326. Epub 2023 Aug 4.

Abstract

In antimalarial drug development research, overcoming drug resistance has been a major challenge for researchers. Nowadays, several drugs like chloroquine, mefloquine, sulfadoxine, and artemisinin are used to treat malaria. But increment in drug resistance has pushed researchers to find novel drugs to tackle drug resistance problems. The idea of using transition metal complexes with pharmacophores as ligands/ligand pendants to show enhanced antimalarial activity with a novel mechanism of action has gained significant attention recently. The advantages of metal complexes include tunable chemical/physical properties, redox activity, avoiding resistance factors, etc. Several recent reports have successfully demonstrated that the metal complexation of known organic antimalarial drugs can overcome drug resistance by showing enhanced activities than the parent drugs. This review has discussed the fruitful research works done in the past few years falling into this criterion. Based on transition metal series (3d, 4d, or 5d), the antimalarial metal complexes have been divided into three broad categories (3d, 4d, or 5d metal-based), and their activities have been compared with the similar control complexes as well as the parent drugs. Furthermore, we have also commented on the potential issues and their possible solution for translating these metal-based antimalarial complexes into the clinic.

Keywords: P. falciparum; antimalarial agents; drug resistance; transition metal complexes.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials* / pharmacology
  • Antimalarials* / therapeutic use
  • Chloroquine / pharmacology
  • Coordination Complexes* / pharmacology
  • Coordination Complexes* / therapeutic use
  • Drug Resistance
  • Humans
  • Malaria* / drug therapy
  • Malaria, Falciparum* / drug therapy
  • Mefloquine / therapeutic use
  • Plasmodium falciparum

Substances

  • Antimalarials
  • Coordination Complexes
  • Chloroquine
  • Mefloquine