Thiourea-functionalized aminoglutethimide derivatives as anti-leishmanial agents.

IF 3.2 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2024-08-02 Epub Date: 2024-07-02 DOI:10.1080/17568919.2024.2359362

Muhammad Sajid, Hina Siddiqui, Humaira Zafar, Sammer Yousuf, Michael D Threadgill, Muhammad Iqbal Choudhary

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Abstract

Aim: We aim to develop new anti-leishmanial agents against Leishmania major and Leishmania tropica.Materials & methods: A total of 23 thiourea derivatives of (±)-aminoglutethimide were synthesized and evaluated for in vitro activity against promastigotes of L. major and L. tropica.Results & conclusion: The N-benzoyl analogue 7p was found potent (IC₅₀ = 12.7 μM) against L. major and non toxic to normal cells. The docking studies, indicates that these inhibitors may target folate and glycolytic pathways of the parasite. The N-hexyl compound 7v was found strongly active against both species, and lacked cytotoxicity against normal cells, whereas compound 7r, with a 3,5-bis-(tri-fluoro-methyl)phenyl unit, was active against Leishmania, but was cytotoxic in nature. Compound 7v was thus identified as a hit for further studies.

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硫脲官能化氨基丁亚胺衍生物作为抗利什曼病药。

目的：我们的目标是开发新的抗利什曼病原体制剂，以对付大利什曼病原体和热带利什曼病原体。材料与方法：合成了 23 种 (±)-aminoglutethimide 的硫脲衍生物，并评估了它们对大利什曼原虫和热带利什曼原虫的体外活性。结果与结论：结果表明，N-苯甲酰基类似物 7p 对大肠杆菌有效（IC50 = 12.7 μM），对正常细胞无毒。对接研究表明，这些抑制剂可能针对寄生虫的叶酸和糖酵解途径。发现 N-己基化合物 7v 对这两种寄生虫都有很强的活性，但对正常细胞没有细胞毒性，而具有 3,5-双（三氟甲基）苯基单元的化合物 7r 对利什曼原虫有活性，但具有细胞毒性。因此，化合物 7v 被确定为有待进一步研究的热门化合物。

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.