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Discovery of Novel Tricyclic Thiazepine Derivatives as Anti-Drug-Resistant Cancer Agents by Combining Diversity-Oriented Synthesis and Converging Screening Approach.

ABSTRACT: An efficient discovery strategy by combining diversity-oriented synthesis and converging cellular screening is described. By a three-round screening process, we identified novel tricyclic pyrido[2,3-b][1,4]benzothiazepines showing potent inhibitory activity against paclitaxel-resistant cell line H460TaxR (EC50 < 1.0 ?M), which exhibits much less toxicity toward normal cells (EC50 > 100 ?M against normal human fibroblasts). The most active hits also exhibited drug-like properties suitable for further preclinical research. This redeployment of antidepressing compounds for anticancer applications provides promising future prospects for treating drug-resistant tumors with fewer side effects.

SUBMITTER: Xiang J

PROVIDER: S-EPMC5592639 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Discovery of Novel Tricyclic Thiazepine Derivatives as Anti-Drug-Resistant Cancer Agents by Combining Diversity-Oriented Synthesis and Converging Screening Approach.

Xiang Jinbao J Zhang Zhuoqi Z Mu Yan Y Xu Xianxiu X Guo Sigen S Liu Yongjin Y Russo Daniel P DP Zhu Hao H Yan Bing B Bai Xu X

ACS combinatorial science 20160415 5

An efficient discovery strategy by combining diversity-oriented synthesis and converging cellular screening is described. By a three-round screening process, we identified novel tricyclic pyrido[2,3-b][1,4]benzothiazepines showing potent inhibitory activity against paclitaxel-resistant cell line H460TaxR (EC50 < 1.0 μM), which exhibits much less toxicity toward normal cells (EC50 > 100 μM against normal human fibroblasts). The most active hits also exhibited drug-like properties suitable for fur ...[more]

PMID: 27082930

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