Faculty of Heath Sciences, School of Pharmacy, North-West University, Potchefstroom 2520, South Africa.
Drug Discovery, Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa.
Eur J Pharm Sci. 2022 Sep 1;176:106242. doi: 10.1016/j.ejps.2022.106242. Epub 2022 Jun 19.
Leishmaniasis is a neglected tropical disease affecting millions of people worldwide, with 650 000 to 1.1 million new infections reported annually by the World Health Organization. Current antileishmanial treatments are unsatisfactory due to the development of parasitic resistance and the toxicity associated with the drugs used, and this highlights the need for the development of new antileishmanial drugs. In this study, a series of nifuroxazide analogues were synthesized in a single step reaction and investigated for their antileishmanial potential. The sulfonate 1l, bearing pyridine ring, was deemed an antileishmanial hit, targeting the amastigotes of Leishmania (L.) donovani and L. major, the pathogens of visceral and cutaneous leishmaniasis, respectively, with micromolar potencies. The benzyl analogues 2c and 2d were also confirmed as submicromolar active leads against amastigotes of L. major. These analogues stand as promising candidates for further investigation involving the evaluation of their in vivo activities and molecular targets.
利什曼病是一种被忽视的热带病，影响着全球数百万人，世界卫生组织每年报告有 65 万至 110 万例新感染病例。由于寄生虫耐药性的发展以及所用药物的毒性，目前的抗利什曼病治疗方法并不令人满意，这凸显了开发新的抗利什曼病药物的必要性。在这项研究中，我们通过一步反应合成了一系列硝呋罗唑类似物，并研究了它们的抗利什曼病潜力。带有吡啶环的磺酸酯 1l 被认为是一种抗利什曼病的命中化合物，针对内脏利什曼病和皮肤利什曼病的病原体利什曼原虫（L.） Donovan 和 L. major 的无鞭毛体具有微摩尔效力。苄基类似物 2c 和 2d 也被证实对 L. major 的无鞭毛体具有亚微摩尔的活性。这些类似物是进一步研究的有前途的候选物，包括评估它们的体内活性和分子靶标。
