2. Academic Validation
  3. Design, synthesis and biological evaluation of VEGFR-2/HDAC dual inhibitors as multitargeted antitumor agents based on fruquintinib and vorinostat

Design, synthesis and biological evaluation of VEGFR-2/HDAC dual inhibitors as multitargeted antitumor agents based on fruquintinib and vorinostat

  • RSC Adv. 2023 Sep 27;13(41):28462-28480. doi: 10.1039/d3ra05542f.
Yali Gao 1,  Fei Li 2 3,  Xin Ni 2,  Siwang Yang 2,  Han Liu 2,  Xingye Wu 2,  Jieqing Liu 2,  Junjie Ma 2
Affiliations

Affiliations

  • 1 Pharmacy Department, The Second Affiliated Hospital of Fujian Medical University Quanzhou 362000 PR China 106204660@qq.com.
  • 2 School of Medicine, Huaqiao University Quanzhou 362000 PR China liujieqing@hqu.edu.cn majunjie3612@hqu.edu.cn.
  • 3 Sinopharm Dongfeng General Hospital, Hubei University of Medicine Shiyan 442008 Hubei PR China.
PMID: 37771923 DOI: 10.1039/d3ra05542f
Abstract

Herein, a series of 4-(benzofuran-6-yloxy)quinazoline derivatives as VEGFR-2/HDAC dual inhibitors were designed and synthesized based on fruquintinib and vorinostat. Among them, compound 13 exhibited potent inhibitory activity against VEGFR-2 and HDAC1 with IC50 values of 57.83 nM and 9.82 nM, and displayed moderate to significant antiproliferative activity against MCF-7, A549, HeLa and HUVEC. The cellular mechanism studies revealed that compound 13 arrested the cell cycle at the S and G2 phases, and induced significant Apoptosis in HeLa cells. Tube formation assay in HUVECs demonstrated that 13 had a significant anti-angiogenic effect. Additionally, a molecular docking study supported the initial design strategy. These results highlighted that 13 was a valuable VEGFR-2/HDAC dual inhibitor and deserved further study for Cancer therapy.

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