Hao, Shu-Yi; Qi, Zhi-Yuan; Wang, Shuai; Wang, Xing-Rong; Chen, Shi-Wu published the artcile< Synthesis and bioevaluation of N-(3,4,5-trimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amines as tubulin polymerization inhibitors with anti-angiogenic effects>, Related Products of 777931-67-6, the main research area is pyridopyrazole trimethoxyaniline palladium acetate catalyst haloalkane Buchwald Hartwig coupling; trimethoxyphenyl pyrazolo pyridinamine preparation antitumor cytotoxicity SAR; Aniogenesis; Antitumor; Inhibitors; Pyrazolo[3,4-b]pyridine; Tubulin polymerization.
A new series of N-(3,4,5-trimethoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-3-amine derivatives I [R1 = H, Me, cyclopentyl; R2 = Me, Et, Pr, etc.] as tubulin polymerization inhibitors were synthesized, and evaluated for the anti-proliferative activities. A structure-activity relationship study revealed that the free amino moiety of 1H-pyrazolo[3,4-b]pyridin-3-amine played an essential role in the anti-proliferative activities. Especially, compound I [R1 = H; R2 = methyl] displayed the strongest anti-proliferation against MCF-7 cells with IC50 value of 0.067 ± 0.003μM, and high selectivity over the normal human embryonic lung WI-38 cells with IC50 value of 23.41 ± 1.53μM. Further mechanistic studies revealed that I [R1 = H; R2 = methyl] showed strong anti-tubulin polymerization activity, changed the morphol. of tubulin, and arrested the cell cycle at the G2/M transition in MCF-7 cells. Mol. docking anal. suggested that I [R1 = H; R2 = methyl] well occupied the colchicine-binding pocket of tubulin. Addnl., I [R1 = H; R2 = methyl] demonstrated anti-angiogenic activities with blocking the migration, invasion and tube formation, disrupting the newly formed tube, and regulating both MMP-9 and TIMP-1 in HUVEC cells. In summary,results highlight that compound I [R1 = H; R2 = methyl] was a potential antitumor compound that was worthy of further development.
Bioorganic & Medicinal Chemistry published new progress about Antiangiogenic agents. 777931-67-6 belongs to class pyridine-derivatives, and the molecular formula is C6H5BrClNO, Related Products of 777931-67-6.