In our study, some newly synthesized aryl-substituted pyrazole derivatives mimicking cis-diphenylethylene scaffold of two apoptotic inducing agents celecoxib and combretastatin A-4 were found to have strong antiproliferative as well as antiinflammatory activities. Among these coxib–combretastatin hybrids, two lead compounds 8 and 6c simultaneously inhibited prostaglandin E2 (PGE2) production in LPS-activated murine macrophage RAW 264.7 cells and suppressed cell cycle progression of MCF7 cells at G2/M or G0/G1 phases, but only compound 8 induced apoptosis via caspase-3 activation. Both the lead compounds showed good docking energies with both protein targets COX-2 and tubulin in the molecule interaction modeling. The cis-diphenylethylene scaffold of celecoxib or combretastatin A-4 as well as functional groups such as the ethyl ester group and the sulfonamide could be considered as potential key features for the dual activity of studied compounds meanwhile the trimethoxybenzene remained the crucial characterization of the newly derived compounds of combretastatins.

在我们的研究中，发现一些新合成的芳基取代的吡唑衍生物模拟了两种凋亡诱导剂塞来昔布和考布他汀 A-4 的顺式-二苯基乙烯支架，具有很强的抗增殖和抗炎活性。在这些 coxib-combretastatin 杂化物中，两种先导化合物8和6c同时抑制 LPS 激活的鼠巨噬细胞 RAW 264.7 细胞中前列腺素 E2 (PGE2) 的产生，并抑制 G2/M 或 G0/G1 期 MCF7 细胞的细胞周期进程，但仅化合物8通过激活 caspase-3 诱导细胞凋亡。在分子相互作用建模中，这两种先导化合物都显示出与蛋白质靶标 COX-2 和微管蛋白的良好对接能量。顺式- 塞来昔布或考布他汀 A-4 的二苯基乙烯支架以及乙酯基团和磺胺等官能团可被认为是研究化合物双重活性的潜在关键特征，同时三甲氧基苯仍然是新衍生化合物的关键表征康布他汀类药物。