Synthesis of New Thiazole-Privileged Chalcones as Tubulin Polymerization Inhibitors with Potential Anticancer Activities.

IF 4.3 3区医学 Q2 CHEMISTRY, MEDICINAL

Pharmaceuticals Pub Date : 2024-08-31 DOI:10.3390/ph17091154

Hamada Hashem, Abdelfattah Hassan, Walid M Abdelmagid, Ahmed G K Habib, Mohamed A A Abdel-Aal, Ali M Elshamsy, Amr El Zawily, Ibrahim Taha Radwan, Stefan Bräse, Ahmed S Abdel-Samea, Safwat M Rabea

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Abstract

A series of novel thiazole-based chalcones were evaluated for their anticancer activity as potential tubulin polymerization inhibitors. In vitro anticancer screening for the thiazole derivatives 2a-2p exhibited broad-spectrum antitumor activity against various cancer cell lines particularly Ovar-3 and MDA-MB-468 cells with a GI₅₀ range from 1.55 to 2.95 μΜ, respectively. Compound 2e demonstrated significant inhibition of tubulin polymerization, with an IC₅₀ value of 7.78 μM compared to Combretastatin-A4 (CA-4), with an IC₅₀ value of 4.93 μM. Molecular docking studies of compounds 2e, 2g, and 2h into tubulin further supported these findings, revealing that they bind effectively to the colchicine binding site, mirroring key interactions exhibited by CA-4. Computational predictions suggested favorable oral bioavailability and drug-likeness for these compounds, highlighting their potential for further development as chemotherapeutic agents.

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作为具有潜在抗癌活性的管蛋白聚合抑制剂的新型噻唑特权查尔酮的合成。

研究人员评估了一系列基于噻唑的新型查耳酮作为潜在的微管蛋白聚合抑制剂的抗癌活性。体外抗癌筛选结果表明，噻唑衍生物 2a-2p 对多种癌细胞株，尤其是 Ovar-3 和 MDA-MB-468 细胞具有广谱抗肿瘤活性，其 GI50 范围分别为 1.55 至 2.95 μΜ。化合物 2e 对微管蛋白聚合有明显的抑制作用，其 IC50 值为 7.78 μM，而 Combretastatin-A4 (CA-4) 的 IC50 值为 4.93 μM。化合物 2e、2g 和 2h 与小管蛋白的分子对接研究进一步证实了这些发现，结果表明它们能有效地与秋水仙碱结合位点结合，与 CA-4 表现出的关键相互作用如出一辙。计算预测表明，这些化合物具有良好的口服生物利用度和药物相似性，突出了它们作为化疗药物进一步开发的潜力。

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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