State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
Bioorg Chem. 2021 Mar;108:104690. doi: 10.1016/j.bioorg.2021.104690. Epub 2021 Feb 2.
Novel withangulatin A (WA) derivatives were synthesized and evaluated for antiproliferative activity against four human cancer cell lines (U2OS, MDA-MB-231, HepG2, and A549). Among these derivatives, 10 exhibited the most potent antiproliferative activity, with an IC value of 74.0 nM against the human breast cancer cell line MDA-MB-231 and potency that was 70-fold that of WA (IC = 5.22 µM). Moreover, 10 caused G2-phase cell cycle arrest in a concentration-dependent manner and induced the apoptosis of MDA-MB-231 cells by increasing intracellular reactive oxygen species (ROS). Compound 10 showed a high selectivity index (SI = 267.03) for breast cancer MDA-MB-231 cells. These results suggest that 10 is a promising anticancer agent.
新型金刚烷 A（WA）衍生物被合成并评估了对四种人癌细胞系（U2OS、MDA-MB-231、HepG2 和 A549）的增殖抑制活性。在这些衍生物中，10 号表现出最强的增殖抑制活性，对人乳腺癌细胞系 MDA-MB-231 的 IC 值为 74.0 nM，活性是 WA 的 70 倍（IC = 5.22 µM）。此外，10 号以浓度依赖的方式引起 G2 期细胞周期阻滞，并通过增加细胞内活性氧物种（ROS）诱导 MDA-MB-231 细胞凋亡。化合物 10 对乳腺癌 MDA-MB-231 细胞表现出高的选择性指数（SI = 267.03）。这些结果表明 10 号是一种很有前途的抗癌剂。
