Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA.
Molecules. 2020 Jul 4;25(13):3063. doi: 10.3390/molecules25133063.
New chrysin-De-allyl-Pac-1 hybrid analogues, tethered with variable heterocyclic systems (-), were rationally designed and synthesized. The target compounds were screened for in vitro antiproliferative efficacy in the triple-negative breast cancer (TNBC) cell line, MDA-MB-231, and normal human mammary epithelial cells (HMECs). Two compounds, and , had the highest efficacy and selectivity towards MDA-MB-231 cells, and thus, were further evaluated by mechanistic experiments. The results indicated that both compounds and induced apoptosis by (1) inducing cell cycle arrest at the G2 phase in MDA-MB-231 cells, and (2) activating the intrinsic apoptotic pathways in a concentration-dependent manner. Physicochemical characterizations of these compounds suggested that they can be further optimized as potential anticancer compounds for TNBC cells. Overall, our results suggest that and could be suitable leads for developing novel compounds to treat TNBC.
新型白杨素-De-烯丙基-Pac-1 杂合类似物，通过可变杂环系统（-）连接，经过合理设计和合成。目标化合物在体外三阴性乳腺癌（TNBC）细胞系 MDA-MB-231 和正常人类乳腺上皮细胞（HMECs）中进行了抗增殖活性筛选。两种化合物（ 和 ）对 MDA-MB-231 细胞具有最高的功效和选择性，因此通过机制实验进一步进行了评估。结果表明，两种化合物（ 和 ）通过（1）诱导 MDA-MB-231 细胞的细胞周期停滞在 G2 期，和（2）以浓度依赖性方式激活内在凋亡途径，诱导细胞凋亡。这些化合物的理化特性表明它们可以进一步优化为治疗 TNBC 细胞的潜在抗癌化合物。总的来说，我们的研究结果表明，化合物（ 和 ）可以作为开发新型化合物治疗 TNBC 的合适先导物。
