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Paper | Regular issue | Vol 104, No. 4, 2022, pp.667-688
Published online, 21st January, 2022
DOI: 10.3987/COM-21-14586
Design, Synthesis and Biological Evaluation of Novel Indole-Containing Sorafenib Derivatives

Sili Fan, Yihong Fu, Siyu Tang, Danping Chen, Zhurui Li, Chengpeng Li, Lihui Shao, Zhenchao Wang,* and Guiping Ouyang*

*College of Pharmacy, Guizhou University, Huaxi St., Guiyang 550025, China


Based on the molecular structure of sorafenib, a series of novel indole (ketone) semicarbazide analogs (1-30) have been designed and synthesized. All new compounds were identified by 1H, 13C NMR and HRMS, and their antiproliferative activity on four cancer cell lines A549, PC-3, K562 and HepG2 were evaluated. In particular, compared with the positive control sorafenib (18.92 μmol/L), compounds 4, 6 and 20 showed two- to three-fold improvement in inhibiting the proliferation of PC-3 cells with IC50 values of 6.75, 8.03 and 8.77 μmol/L respectively. In vitro activity evaluation experiments showed that compound 6 could significantly inhibit the proliferation and colony formation of PC-3 cells, induce apoptosis and arrest the cells in the G2/M phase. Finally, western blot speculated that compound 6 may affect the signal transduction of downstream signaling pathway PI3K/Akt by affecting EGFR protein and autophosphorylation thereby promoting cell apoptosis and inhibiting cell growth. These results provide important information for the development of new anti-cancer drugs.