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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 1: 95 - 107

DOI: https://doi.org/10.6023/cjoc201908021

Design, Synthesis and Biological Evaluation of Novel (Quinolinyl-3-pyridinyl)benzenesulfonamide-Based Hydroxamic Acids as PI3K and HDAC Dual Targeting Inhibitors

  • Gu Yiyu ,
  • Lü Xiaoqing ,
  • Ma Xiaodong ,
  • Zhang Haojian ,
  • Ji Yuanyuan ,
  • Ding Wanjing ,
  • Shen Li
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  • a Ocean College, Zhejiang University, Zhoushan, Zhejiang 316021;
    b College of Medicine, Jiaxing University, Jiaxing, Zhejiang 314001;
    c School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012

Received date: 2019-08-13

  Revised date: 2019-09-05

  Online published: 2019-09-18

Supported by

Project supported by the National Natural Science Foundation for Young Scientists of China (No. 81402845) and the Foundation for the Science and Technology Project of Zhoushan City (No. 2018C81035).

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Abstract

Polypharmacology has emerged as a promising approach to drug discovery, especially antitumor drug. This study reports the design, synthesis, and biological evaluation of novel phosphatidylinositol 3-kinases (PI3Ks) and histone deacetylases (HDACs) dual inhibitors on the basis of GSK2126458 under clinical evaluation and vorinostat approved. Among these hybrid molecules, GYB-4 and GYB-5 possessed potent inhibition against both PI3Kα (1.0 and 1.3 nmol/L, respectively) and HDAC1 (4.2 and 4.8 nmol/L, respectively). Antiproliferative assays with HCT116, PC3 and A2780 cell lines subsequently were performed. The structure-activity relationship study will guide to optimization of dual PI3K and HDAC inhibitors.

Key words： phosphatidylinositol 3-kinases (PI3K); histone deacetylases (HDAC); dual targeting inhibitor; bioactivity

Cite this article

Gu Yiyu , Lü Xiaoqing , Ma Xiaodong , Zhang Haojian , Ji Yuanyuan , Ding Wanjing , Shen Li . Design, Synthesis and Biological Evaluation of Novel (Quinolinyl-3-pyridinyl)benzenesulfonamide-Based Hydroxamic Acids as PI3K and HDAC Dual Targeting Inhibitors[J]. Chinese Journal of Organic Chemistry, 2020 , 40(1) : 95 -107 . DOI: 10.6023/cjoc201908021

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