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.

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新型喹唑啉酮衍生物的合成及体外抗利什曼病作用

目前用于治疗利什曼病的药物有几个缺点，包括高毒性、需要住院的药物给药以及寄生虫对临床使用药物的耐药性的出现。因此，迫切需要开发安全、负担得起且有效的新型抗利什曼病药物。在这项研究中，通过评估两种新系列合成喹唑啉酮衍生物对利什曼原虫( L. ) donovani和L. Major 的活性，研究它们作为未来潜在的抗利什曼原虫物种。这些衍生物的细胞毒性特征在 Vero 细胞上进行了体外评估。与参考药物卤夫酮（febrifugine 的临床衍生物）相比，发现这些化合物更安全，并且对哺乳动物细胞没有任何毒性活性。然而，他们已证明抗利什曼原虫生长抑制效果不佳。已发现活性最强的两种化合物是单喹唑啉酮2d和双喹唑啉酮5b，对L. Major和L. donovani 9515 前鞭毛体的生长抑制效力分别为 35% 和 29% 。这些结果建议重新设计结构，尤其是 在喹唑啉酮环上包含极性基团，以潜在地产生新型喹唑啉酮衍生物，赋予有效的抗利什曼病潜力。