Phenylurenyl benzamide Analogues as a New Anti-malarial Chemotype that Potently Kill Chloroquine Resistant Parasite

Abstract

The growing resistance against current anti-malarial drugs represents a major health challenge, thus necessitating the development of new chemotypes targeting the malaria parasite at different stages of development. We have synthesized different phenylurenyl benzamide analogues, by the reaction of anthranilamide with different phenyl isocyanate/ isothiocyanates in a single step. These compounds in the initial in vitro assay show significant inhibitory activity over the growth of Plasmodium falciparum. Two of the derivatives, RTK41 and 43 were more potent inhibitors compared to others. The potent compounds were tested in vitro on a chloroquine-resistant strain of P. falciparum, which also showed significant growth inhibition. These compounds are found to be non-toxic to the mammalian cells. These results suggest that phenylurenyl bezamide analogues are a promising class of potent anti-malarial chemotypes.