2. Academic Validation
  3. Discovery of novel benzofuro[3,2-b]quinoline derivatives as dual CDK2/Topo I inhibitors

Discovery of novel benzofuro[3,2-b]quinoline derivatives as dual CDK2/Topo I inhibitors

  • Bioorg Chem. 2022 Sep;126:105870. doi: 10.1016/j.bioorg.2022.105870.
Yaoguang Huang 1,  Wenwu Liu 1,  Shuoqi Huang 2,  Deping Li 3,  Chang Xu 2,  Xiaowen Jiang 4,  Mingyue Liu 2,  Xin Liu 2,  Chengze Zhu 3,  Limeng Wu 1,  Huanhua Chen 1,  Zihua Xu 5,  Qingchun Zhao 6
Affiliations

Affiliations

  • 1 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
  • 2 School of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
  • 3 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
  • 4 Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, People's Republic of China.
  • 5 Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, People's Republic of China; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: [email protected].
  • 6 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, People's Republic of China; School of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Electronic address: [email protected].
PMID: 35636125 DOI: 10.1016/j.bioorg.2022.105870
Abstract

Uncontrolled cell proliferation is a hallmark of Cancer. The major regulator of the cell cycle, cyclin dependent kinase 2 (CDK2), has become a mature target for Cancer treatment. Herein, we describe our efforts toward the discovery of a series of benzofuro[3,2-b]quinoline alkaloid derivatives as CDK2 inhibitors through a scaffold hopping strategy. Compound ZLHQ-5f has Topoisomerase I (Topo I) inhibitory activity due to the unique structure of benzofurano[3,2-b]quinoline. Resultantly, ZLHQ-5f exhibited promising anti-proliferative and CDK2 inhibitory activities. It also arrests the cell cycle in S-phase, triggers Apoptosis in HCT116 cells, and has a good safety profile in vivo. There has yet to be a report on dual CDK2/Topo I Inhibitor, thus this will be a novel attempt.

Keywords

Benzofuro[3,2-b]quinoline alkaloid; CDK2; Cancer; Topo I.

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