Novel multi-target angiogenesis inhibitors as potential anticancer agents: Design, synthesis and preliminary activity evaluation

Bioorg Chem. 2024 Feb 14;145:107211. doi: 10.1016/j.bioorg.2024.107211. Online ahead of print.ABSTRACTBased on the crucial role of histone deacetylase (HDAC) and receptor tyrosine kinase in angiogenesis, in situ assembly, skeletal transition, molecular hybridization, and pharmacophore fusion were employed to yield seventy-six multi-target angiogenesis inhibitors. Biological evaluation indicated that most of the compounds exhibited potent proliferation inhibitory activity on MCF-7 cells, with the TH series having the highest inhibitory activity on MCF-7 cells. In addition, the IC50 values of TA11 and TH3 against HT-29 cellswere 0.078 μmol/L and 0.068 μmol/L, respectively. The cytotoxicity evaluation indicated that TC9, TA11, TM4, and TH3 displayed good safety against HEK293T cells. TH2 and TH3 could induce apoptosis of MCF-7 cells. Molecular modeling and ADMET prediction results indicated that most of target compounds showed promising medicinal properties, which was consistent with the experimental results. Our findings provided new lead compounds for the structural optimization of multi-target angiogenesis inhibitors.PMID:38364550 | DOI:10.1016/j.bioorg.2024.107211

Source: Bioorganic Chemistry - February 16, 2024 Category: Chemistry Authors: Qingqing Zhang Zilong Li Junyu Zhang Yanchen Li Xiaoyan Pan Jingkun Qu Jie Zhang Source Type: research