Identifying a novel anticancer agent with microtubule-stabilizing effects through computational cell-based bioactivity prediction models and bioassays

作者：Luo Yao; Zeng Ranran; Guo Qingqing; Xu Jianrong; Sun Xiaoou^*; Wang Ling^*

来源：Organic and Biomolecular Chemistry, 2019, 17(6): 1519-1530.

DOI：10.1039/c8ob02193g

We report the identification of 14 novel anticancer agents through established computational anticancer cell-based models. Among these novel hits, the compound G03 exhibits stronger inhibitory effects on the proliferation of MCF-7, HepG2, MDA-MB-231, HCTT116, and HeLa as compared with the FDA-approved sorafenib, with IC50 values of 4.61, 3.20, 2.82, 2.98, and 2.90 mu M, respectively. The tubulin protein was validated to be a target of G03 using SPR, tubulin polymerization, immunofluorescence, and western blot assays. G03 is a novel structurally simple anticancer agent with unusual microtubule-stabilizing effects. Our study demonstrated the identification of bioactive small molecules by computational phenotypic modeling, which represents a feasible route toward innovative leads for chemical biology and medicinal chemistry.

• 单位
  河北医科大学; 华南理工大学; 上海交通大学