A series of novel steroidal-chalcone derivates were designed and synthesized based on the molecular hybridization strategy and further evaluated for their growth inhibitory activity against three human cancer cell lines. The MTT results indicated that most compounds were apparently more sensitive to human breast cancer cells MDA-MB-231. Compounds 8 and 18 exerted the best cytotoxic activity against triple-negative MDA-MB-231 cells with the IC₅₀ values of 0.42 μM and 0.52 μM respectively, which were 23-fold increase or more compared with 5-Fu. Further mechanism studies demonstrated that compound 8 could induce cells apoptosis through regulating Bcl-2/Bax proteins and activating caspase-3 signaling pathway. Moreover, compound 8 could upregulate the cellular ROS levels which accelerated the apoptosis of MDA-MB-231 cells. In addition, interestingly, cell cycle assay showed that compound 8 could arrest MDA-MB-231 cells at S phase but not commonly anticipated G2/M phase. These evidences fully confirmed that compound 8 could be a potential candidate that deserves further development as an antitumor agent against triple-negative breast cancer.

基于分子杂交策略设计和合成了一系列新型甾体-查尔酮衍生物，并进一步评估了它们对三种人类癌细胞系的生长抑制活性。MTT结果表明，大多数化合物显然对人乳腺癌细胞MDA-MB-231更敏感。化合物8和18对三阴性MDA-MB-231细胞表现出最佳的细胞毒活性，IC ₅₀值分别为0.42μM和0.52μM，与5-Fu相比增加23倍或更多。进一步的机理研究表明，化合物8通过调节Bcl-2 / Bax蛋白和激活caspase-3信号通路可以诱导细胞凋亡。此外，化合物8可以上调细胞ROS水平，从而加速MDA-MB-231细胞的凋亡。另外，有趣的是，细胞周期测定法表明化合物8可以将MDA-MB-231细胞阻滞在S期，而不是通常预期的G2 / M期。这些证据充分证实了化合物8作为抗三阴性乳腺癌的抗肿瘤药可能是值得进一步发展的潜在候选物。