Rationale, in silico docking, ADMET profile, design, synthesis and cytotoxicity evaluations of phthalazine derivatives as VEGFR-2 inhibitors and apoptosis inducers.

ABSTRACT: New phthalazine derivatives as vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors were synthesized joined to different spacers including pyrazole, α,β-unsaturated ketonic fragment, pyrimidinone and/or pyrimidinthione. A docking study was carried out to explore the suggested binding orientations of the novel derivatives inside the active site of VEGFR-2. The obtained biological data were extremely interrelated to that of the docking study. In particular, compounds 4b and 3e showed the highest activities against Michigan Cancer Foundation-7 (MCF-7) and Hepatocellular carcinoma G2 (HepG2) with half maximal inhibitory concentration (IC₅₀) = 0.06, 0.06 μM and 0.08, 0.19 μM respectively. Our derivatives 3a-e, 4a,b and 5a,b were evaluated for their cytotoxicity against

SUBMITTER: Bayoumi HH 

PROVIDER: S-EPMC11348385 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature