Vishnuvardhan M V P S, V Saidi Reddy, Chandrasekhar Kunta, Lakshma Nayak V, Sayeed Ibrahim Bin, Alarifi Abdullah, Kamal Ahmed
Medicinal Chemistry and Pharmacology , CSIR-Indian Institute of Chemical Technology , Tarnaka , Hyderabad 500007 , India . Email:
Catalytic Chemistry Research Chair , Chemistry Department , College of Science , King Saud University , Riyadh 11451 , Saudi Arabia.
Medchemcomm. 2017 Jul 18;8(9):1817-1823. doi: 10.1039/c7md00273d. eCollection 2017 Sep 1.
A series of new triazolo linked 4β-amidopodophyllotoxin conjugates () were synthesized using click chemistry and evaluated for their antitumor activity against four human cancer cell lines. Among them, two compounds ( and ) showed significant anticancer activity with IC values of 0.9 and 0.07 μM, respectively. Biological studies are conducted into the cell-cycle distribution of these conjugates inducing G2/M-phase arrest, apart from an increase in the levels of caspase-3 proteins, followed by apoptotic cell death. A tubulin polymerization assay analysis showed that these compounds effectively inhibit microtubule assembly in HeLa cells and, moreover, Hoechst 33258 and Immunohistochemistry staining suggest that these compounds induce cell death by apoptosis. The docking studies showed that compounds and interact and bind efficiently with the tubulin protein at the colchicine site.
利用点击化学合成了一系列新的三唑连接的4β-氨基鬼臼毒素缀合物（），并评估了它们对四种人类癌细胞系的抗肿瘤活性。其中，两种化合物（和）表现出显著的抗癌活性，IC值分别为0.9和0.07μM。除了半胱天冬酶-3蛋白水平增加，随后发生凋亡性细胞死亡外，还对这些缀合物诱导G2/M期阻滞的细胞周期分布进行了生物学研究。微管蛋白聚合试验分析表明，这些化合物可有效抑制HeLa细胞中的微管组装，此外，Hoechst 33258和免疫组织化学染色表明这些化合物通过凋亡诱导细胞死亡。对接研究表明，化合物和在秋水仙碱位点与微管蛋白有效相互作用并结合。
