Design, synthesis and biological evaluation of VEGFR-2/HDAC dual inhibitors as multitargeted antitumor agents based on fruquintinib and vorinostat
Yali Gao, Fei Li, Xin Ni, Siwang Yang, Han Liu, Xingye Wu, Jie‐Qing Liu, Junjie Ma
Abstract
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.
Topics & Concepts
VorinostatChemistryDual (grammatical number)VEGF receptorsHistone deacetylasePharmacologyCombinatorial chemistryCancer researchMedicineHistoneBiochemistryGeneArtLiteratureHistone Deacetylase Inhibitors ResearchAngiogenesis and VEGF in CancerProtein Degradation and Inhibitors