Synthesis, Structure-Activity Relationship Studies and Biological Evaluation of Novel 2,5-Disubstituted Indole Derivatives as Anticancer Agents.

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Hu H, Wu J, Ao M, Wang H, Zhou T, Xue Y, Qiu Y, Fang M, Wu Z,

Hu H, Wu J, Ao M, Wang H, Zhou T, Xue Y, Qiu Y, Fang M, Wu Z, (click to view)

Hu H, Wu J, Ao M, Wang H, Zhou T, Xue Y, Qiu Y, Fang M, Wu Z,

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Chemical biology & drug design 2016 6 18() doi 10.1111/cbdd.12808


Three novel series of 2,5-disubstituted indole derivatives were synthesized and evaluated in vitro for their anti-proliferative activity against human cancer cells and HIV-1 inhibition activity used as a read-out of cellular activity. Most compounds were found to have potent anticancer activity. In particular, 2c and 3b which showed effectively to repress HIV-1 transcription had a pan anti-proliferative activity in cervical cancer cells (Hela), breast cancer cells (MCF-7), liver cancer cells (HepG2) and lung cancer cells (H460 and A549). While 3b exhibited high sensitivity to A549 cells with the IC50 value 0.48±0.15 μM, 2c showed high selectivity toward HepG2 cells with the IC50 value 13.21±0.30 μM. With respect to the cellular mechanism of action, HepG2 cells treated with 2c and A549 cells treated with 3b for 24 hours were studied by annexin V/PI staining and western blot analysis, and results revealed that 2c and 3b may induce cancer cells apoptosis through inhibiting the phosphorylation at Ser2 of RNAPII CTD which can be phosphorylated by cyclin-dependent kinase 9. These studies indicated that 2c and 3b may develop as potent lead compounds in the therapy of cancer. However, determining their roles in preventing HIV-1 still requires further intensive study. This article is protected by copyright. All rights reserved.

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