In a search for new drug candidates for one of the neglected tropical diseases, leishmaniasis, twenty quinoline-isatin hybrids were synthesized and tested for their in vitro antileishmanial activity against Leishmania major strain. All the synthesized compounds showed promising in vitro activity against the promastigote form in a low micromolar range (IC₅₀ = 0.5084–5.9486 μM) superior to the reference miltefosine (IC₅₀ = 7.8976 μM). All the target compounds were then tested against the intracellular amastigote form and showed promising inhibition effects (IC₅₀ = 0.60442–8.2948 μM versus 8.08 μM for miltefosine). Compounds 4e, 4b and 4f were shown to possess the highest antileishmanial activity against both promastigote and amastigote forms. The most active compounds were proven to exhibit their significant antileishmanial effects through antifolate mechanism, targeting DHFR-TS and PTR1. To evaluate the safety profile of the most active derivatives 4e, 4b and 4f, the in vitro cytotoxicity test was carried out and displayed higher selectivity indices than the reference miltefosine. Molecular docking within putative target protein PTR1 confirmed the high potentiality of the most active compounds 4e, 4b and 4f to block the catalytic activity of Lm-PTR1.

在寻找一种被忽视的热带疾病利什曼病的新候选药物时，合成了 20 种喹啉-靛红杂化物，并测试了它们对利什曼原虫主要菌株的体外抗利什曼原虫 活性。所有合成的化合物在低微摩尔范围内 (IC ₅₀  = 0.5084–5.9486 μM) 均显示出优于参考米替福新 (IC _{50 = 7.8976 μM) 的有前途}的体外活性 。然后针对细胞内无鞭毛体形式测试所有目标化合物，并显示出有希望的抑制作用（IC ₅₀  = 0.60442–8.2948 μM 对比米替福新 8.08 μM）。化合物4e , 4b和4f显示出对前鞭毛体和无鞭毛体形式具有最高的抗利什曼动物活性。事实证明，最活跃的化合物通过抗叶酸机制显示出显着的抗犬类动物作用，靶向 DHFR-TS 和 PTR1。为了评估最具活性的衍生物4e、4b和4f 的安全性，进行了体外细胞毒性试验并显示出比参比米替福新更高的选择性指数。假定靶蛋白 PTR1 内的分子对接证实了最具活性的化合物4e、4b和4f具有阻断 Lm-PTR1 催化活性的高潜力。