Molecular hybridization approach is a promising structural modification tool to design new chemical entities (NCEs) by mimicking two different pharmacophoric units into one scaffold to enhance the biological properties. With this aim, combretastatin-A4 acids were integrated with sulfonyl piperazine scaffolds as a one molecular platform and evaluated for their in vitro antiproliferative activity against a panel of human cancer lines cell lines namely, lung (A549), mouse melanoma (B16F10), breast (MDA MB-231and MCF-7) and colon (HCT-15) by MTT assay. Amongst which the compound (E)-3-(4-Chlorophenyl)-1-(4-((4-chlorophenyl)sulfonyl)piperazin-1-yl)-2-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (5 ab) displayed significant IC50 values in the range of 0.36 to 7.08 μm against the selected cancer cell lines. Moreover, 5 ab was found to be the most potent member of this series with IC50 0.36±0.02 μm. Further investigations revealed that the compound 5 ab displayed significant inhibition of tubulin assembly with IC50 5.24±0.06 μm and molecular docking studies also disclosed the binding of 5 ab effectively in CA4 binding space at the colchicine binding site. The flow cytometric analysis demonstrated that the compound 5 ab caused cell cycle arrest at G2/M phase in A549 cells. Compound 5 ab induced apoptosis in A549 cells which was further evaluated by different staining assays such as DAPI and AO which undoubtedly speculated, the induction of apoptosis. To study the anti-migration with 5 ab, cell migration/scratch wound assay was performed and the extent of apoptosis was studied by Annexin-V, including mitochondrial potential by JC-1 staining.

中文翻译：

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通过分子杂交方法合成模拟磺酰哌嗪的Combretastatin-A4羧酰胺类：体外细胞毒性评估和微管蛋白聚合的抑制作用。

分子杂交方法是一种有前途的结构修饰工具，可通过将两个不同的药效团单元模拟到一个支架中来设计新的化学实体（NCE），以增强生物学特性。为此，将康维他汀-A4酸与磺酰哌嗪支架整合为一个分子平台，并评估了其对一组人类癌症细胞系，即肺（A549），小鼠黑素瘤（B16F10），乳腺的体外抗增殖活性。 （MTA MB-231和MCF-7）和结肠（HCT-15）进行MTT分析。其中化合物（E）-3-（4-氯苯基）-1-（4-（（4-氯苯基）磺酰基）哌嗪-1-基）-2-（3,4,5-三甲氧基苯基）prop-2 -en-1-one（5 ab）对选定的癌细胞系显示出显着的IC50值，范围为0.36至7.08μm。而且，发现5 ab是该系列中最有效的成员，IC50为0.36±0.02μm。进一步的研究表明，化合物5 ab表现出对微管蛋白组装的显着抑制，IC50为5.24±0.06μm，并且分子对接研究还揭示了5 ab在秋水仙碱结合位点的CA4结合空间有效结合。流式细胞仪分析表明，化合物5ab引起A549细胞中G2 / M期的细胞周期停滞。化合物5ab诱导了A549细胞的凋亡，这可以通过不同的染色测定法如DAPI和AO进一步评估，所述染色测定法毫无疑问地推测了细胞凋亡的诱导。为了研究5 ab的抗迁移，进行了细胞迁移/划伤伤口测定，并通过Annexin-V研究了细胞凋亡的程度，包括通过JC-1染色的线粒体电位。