以激酶纺锤体蛋白为靶点的喹啉衍生物的结构导向研究。

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-05-15 DOI:10.1016/j.bmcl.2025.130278

Rohini S. Kavalapure , Shankar G. Alegaon , Shankar Gharge , Shriram D. Ranade , Sachin Gudasi , U. Venkatasubramanian , Soundarya Priya A.

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引用次数: 0

摘要

由于运动蛋白Eg5在有丝分裂中起着至关重要的作用，它是癌症治疗的一个有希望的靶点。本研究设计并评价了2-（（7-氯喹啉-4-基）氨基）苯并肼衍生物作为Eg5抑制剂。化合物6d和6e对MCF-7细胞具有较强的抑制作用（IC50分别为1.519 ± 0.4415 μM和0.2848 ± 0.070 μM）和显著的抗增殖活性。药效团模型、对接、MD模拟和MM/GBSA分析证实了Eg5活性位点内稳定的相互作用。这些化合物还调节乳腺癌相关通路，包括PI3K-Akt和MAPK。这些发现强调了化合物6d和6e是有希望的抗癌药物，需要进一步的体内研究来验证它们的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Structure-guided development of Quinoline derivatives targeting kinesin spindle protein

The kinesin Eg5 protein is a promising target for cancer therapy due to its crucial role in mitosis. This study designed and evaluated 2-((7-chloroquinolin-4-yl) amino) benzohydrazide derivatives as Eg5 inhibitors. Compounds 6d and 6e exhibited potent inhibition (IC₅₀: 1.519 ± 0.4415 μM and 0.2848 ± 0.070 μM, respectively) and significant antiproliferative activity against MCF-7 cells. Pharmacophore modeling, docking, MD simulations, and MM/GBSA analyses confirmed stable interactions within the Eg5 active site. These compounds also modulate breast cancer-related pathways, including PI3K-Akt and MAPK. These findings highlight compounds 6d and 6e as promising anticancer agents, warranting further in vivo studies to validate their therapeutic potential.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.