A series of naphthalene-chalcone derivatives (3a-3t) were prepared and evaluated as tubulin polymerisation inhibitor for the treatment of breast cancer. All compounds were evaluated for their antiproliferative activity against MCF-7 cell line. The most of compounds displayed potent antiproliferative activity. Among them, compound 3a displayed the most potent antiproliferative activity with an IC50 value of 1.42 ± 0.15 µM, as compared to cisplatin (IC50 = 15.24 ± 1.27 µM). Additionally, the promising compound 3a demonstrated relatively lower cytotoxicity on normal cell line (HEK293) compared to tumour cell line. Furthermore, compound 3a was found to induce significant cell cycle arrest at the G2/M phase and cell apoptosis. Compound 3a displayed potent tubulin polymerisation inhibitory activity with an IC50 value of 8.4 µM, which was slightly more active than the reference compound colchicine (IC50 = 10.6 µM). Molecular docking analysis suggested that 3a interact and bind at the colchicine binding site of the tubulin.

中文翻译：

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靶向微管蛋白秋水仙碱结合位点的新型萘-查尔酮衍生物作为MCF-7乳腺癌细胞上潜在的抗癌剂的合成，生物学评估和分子建模。

制备了一系列萘-查耳酮衍生物（3a-3t），并将其评估为微管蛋白聚合抑制剂，用于治疗乳腺癌。评价所有化合物对MCF-7细胞系的抗增殖活性。大多数化合物显示出有效的抗增殖活性。其中，与顺铂相比，化合物3a具有最强的抗增殖活性，IC50值为1.42±0.15 µM（IC50 = 15.24±1.27 µM）。另外，与肿瘤细胞系相比，有希望的化合物3a在正常细胞系（HEK293）上表现出相对较低的细胞毒性。此外，发现化合物3a在G2 / M期诱导明显的细胞周期停滞和细胞凋亡。化合物3a显示出有效的微管蛋白聚合抑制活性，IC50值为8.4 µM，其活性比参考化合物秋水仙碱略高（IC50 = 10.6 µM）。分子对接分析表明3a在微管蛋白的秋水仙碱结合位点相互作用并结合。