Advances in the Potential of Quinoline-Derived Metal Complexes as Antimalarial Agents: A Review

Abstract

Quinolines obtained from native trees of South and Central America, of the genus Cinchona, have been used since the 17th century for the treatment of malaria. However, it was only in 1820 that quinine had its structure elucidated, and subsequently, during the 20th century, several synthetic derivatives were produced with quinine superior activities. In parallel, the search for the synthesis of metal complex compounds for the treatment of malaria dates from 1994, with the development of ferroquine, an iron complex derived from chloroquine, developed by Biot and collaborators at Lille University. After, there are several metal complexes synthesized from quinine with various metals, such as ruthenium, gold, iridium, and platinum, over the last 30 years, which are the aims of this review. This review identified 84 quinoline–metal complexes reported across 25 studies, with the gold complex (Complex 63) showing significant potency against the FcBI strain (IC₅₀ 10 nM), outperforming chloroquine (CQ, 50 nM), indicating that metal coordination enhances the drug's action. The ruthenium complex (Complex 03) exhibited activity against PFB but was less effective than CQ (IC₅₀ 22.5 vs. 8.2 nM). Other complexes, such as Au(III) (Complex 61), Ir(I) (Complex 52), and Ir(II) (Complex 50), also demonstrated promising results with varying effectiveness across different strains. Structural features, including linear geometry in Au(I) complexes and square planar or piano stool geometries in Ru(II) and Ir complexes, play crucial roles in influencing their biological activity. These findings highlight the potential of metal coordination in improving antimalarial efficacy.