Synthesis and in vitro antileishmanial efficacy of novel quinazolinone derivatives

Abstract

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 the Leishmania (L.) donovani and L. major species. 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 quinazolinone 2d and the bisquinazolinone 5b with growth inhibitory efficacies of 35% and 29% for the L. major and L. donovani 9515 promastigotes, respectively. These outcomes had suggested structural redesign, inter alia the inclusion of polar groups on the quinazolinone ring, to potentially generate novel quinazolinone derivatives, endowed with effective antileishmanial potential.

Medicinal perspective of quinazolinone derivatives: Recent developments and structure–activity relationship studies

“…Quinethazone is another quinazolinone moiety–containing marketed diuretic drug used to treat hypertension by inhibiting Na + /Cl − reabsorption from the distal convoluted tubules in the kidneys. Balaglitazone is an antidiabetic drug that contains a quinazolinone ring as well as a thiazolidinedione heterocyclic ring and is used to help patients with type 2 diabetes maintain blood glucose levels [10]. Tiacrilast is an allergic mediator release inhibitor.…”

Synthesis, antileishmanial, antimalarial evaluation and molecular docking study of some hydrazine-coupled pyrazole derivatives

“…Globally, nearly 350 million people are at risk of leishmaniasis. The overall prevalence of leishmaniasis in the world is 12 million [ 3 ]. For instance, visceral leishmaniasis (VL) was implicated in approximately 6% (1.4 million) of all disability-adjusted life-years (DALYs) caused by NTDs in 2015 [ 2 ], echoing the economic implication of leishmaniasis in low- and middle-income countries.…”

Synthesis, antileishmanial, antimalarial evaluation and molecular docking study of some hydrazine-coupled pyrazole derivatives

“…The estimated prevalence of all forms of leishmaniasis in the world is 12 million [3]. For instance, visceral leishmaniasis (VL) was implicated in approximately 6% (1.4 million) of all disability-adjusted life-years (DALYs) caused by NTDs in 2015 [2], echoing the economic implication of leishmaniasis in low-and middle-income countries.…”