2. Academic Validation
  3. Design, synthesis and biological evaluation of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates containing sulfonamido as potential PI3Kα inhibitors

Design, synthesis and biological evaluation of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates containing sulfonamido as potential PI3Kα inhibitors

  • Bioorg Med Chem. 2019 Jun 1;27(11):2261-2267. doi: 10.1016/j.bmc.2019.04.021.
Yong Yin 1,  Jia-Qin Hu 2,  Xu Wu 3,  Shao Sha 3,  She-Feng Wang 3,  Fang Qiao 3,  Zhong-Cheng Song 4,  Hai-Liang Zhu 5
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China; The Joint Research Centre of Gene Interference, Guangzhou University and Keele University for Gene Interference and Application, School of Life Science, Guangzhou University, 230 Waihuan West Road, Guangzhou 510006, People's Republic of China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
  • 4 School of Chemistry & Environmental Engineering, Jiangsu University of Technology, 1801 Zhongwu Rd., Changzhou, Jiangsu 213001, People's Republic of China. Electronic address: songzhongcheng@jsut.edu.cn.
  • 5 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
PMID: 31029551 DOI: 10.1016/j.bmc.2019.04.021
Abstract

A series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates contained sulfonamido were designed and synthesized, and their Anticancer effects in vitro was evaluated to develop some new PI3Kα inhibitors. Most of desired compounds exhibited the better antiproliferative activities against four Cancer cell lines than that of LY294002. Out of them, compound 4o displayed the potent antiproliferative activity and high selectivity against the PI3Kα protein and it can induce Apoptosis of HCT116 in a dose-dependent manner. Western blot assay indicated that compound 4o obviously down-regulated expression of p-Akt (S473). Molecular docking was performed to clarify the possible binding mode between compound 4o and PI3Kα. All these results indicated that compound 4o could be a potential inhibitor of PI3Kα.

Keywords

Anticancer; Chromeno[4,3-c]pyrazol-4(2H)-one derivates; Molecular docking; PI3Kα.

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