Abstract
We, herein, report the structural optimization of 1,2,5-substituted pyrroles for developing a novel kind of vascular endothelial growth factor receptor (VEGFR) inhibitors. 4-Methoxy-N-((1-(prop-2-yn-1-yl)-1H-pyrrol-2-yl)methyl) aniline (20) was the most potent VEGFR inhibitor (IC50 = 4.7 µM, Ka 3.6 × 103 M−1) among the series of compounds screened here. It exhibited almost 100% tumor growth inhibition over the 60 human cancer cell lines panel and displayed GI50 2.94, 8.54, 16 and 14.2 µM against non-small cell lung cancer (HOP-92), renal cancer (A498), prostate cancer (PC-3) and breast cancer (MDA-MB-468) cell lines, respectively. Notably, compound 20 binds in the ATP-binding region of VEGFR that probably prevents the phosphorylation process and inhibits the downstream angiogenesis-promoting signal cascade. Collectively, 20 is identified as a potent candidate for its development as a new antiangiogenic agent.
Published Version
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