Heteroleptic Rh(III) phenylpyridyl complexes based on an aminoquinoline-benzimidazole hybrid scaffold: Antiplasmodial evaluation and mechanistic insights

A small series of cationic Rh(III) polypyridyl aminoquinoline-benzimidazole hybrid complexes were syn-thesised and evaluated for their in vitro antiplasmodial activity against the chloroquine-sensitive (NF54) and multi-drug resistant (K1) strains of the human malaria parasite, Plasmodium falciparum. In general, the hybrid complexes display good activity against the chloroquine-sensitive (NF54) strain of P. falciparum, maintaining activity against the multidrug-resistant (K1) strain, with low to no cytotoxicity against the Chinese hamster ovarian cell line. Selected active hybrid complexes demonstrated significant inhibition of beta-haematin formation in a cell-free NP-40 assay. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

In this study, a series of cationic Rh(III) polypyridyl aminoquinoline-benzimidazole hybrid complexes were synthesized and evaluated for their in vitro antiplasmodial activity. The hybrid complexes showed good activity against the chloroquine-sensitive strain of Plasmodium falciparum and maintained activity against the multidrug-resistant strain, with low to no cytotoxicity. Selected active hybrid complexes also demonstrated significant inhibition of beta-haematin formation.