Synthesis and in vitro antileishmanial efficacy of novel quinazolinone derivatives

Currently available drugs being used to treat leishmaniasis have several shortcomings, including high toxicity, drug administration that requires hospitalization, and the emergence of parasite resistance against clinically used drugs. As a result, there is a dire need for the development of new antileishmanial drugs that are safe, affordable, and efficient. In this study, two new series of synthesized quinazolinone derivatives were investigated as potential future antileishmanial agents, by assessing their activities against theLeishmania(L.)donovaniandL. majorspecies. The cytotoxicity profiles of these derivatives were assessed in vitro on Vero cells. The compounds were found to be safer and without any toxic activities against mammalian cells, compared to the reference drug, halofuginone, a clinical derivative of febrifugine. However, they had demonstrated poor antileishmanial growth inhibition efficacies. The two compounds that had been found the most active were the mono quinazolinone2dand the bisquinazolinone5bwith growth inhibitory efficacies of 35% and 29% for theL. majorandL. donovani9515 promastigotes, respectively. These outcomes had suggested structural redesign,inter aliathe inclusion of polar groups on the quinazolinone ring, to potentially generate novel quinazolinone derivatives, endowed with effective antileishmanial potential.

Automated summary

Current drugs for leishmaniasis treatment have limitations such as high toxicity and emerging resistance, necessitating the development of new, safe, and effective medications. Two new series of synthesized quinazolinone derivatives were assessed for potential antileishmanial properties. While less toxic to mammalian cells compared to halofuginone, the compounds showed modest antileishmanial efficacy, suggesting the need for further structural optimization.