Design, one-pot sequential synthesis and molecular docking study of novel diaryl urea derivatives as potential anti-carcinoma agents

One-pot reaction as a part of “green chemistry” approach using short cycles of design–make–test provide efficient synthetic pathway for drug discovery and development. The diarylureascaffold has been used widely to design potential anticancer agents due to its important role inangiogenesis which regulates by many growth factors such as the vascular endothelial growthfactors (VEGFs) and receptor (VEGFR-۲). In order to optimization of sorafenib ,a VEGFR۲inhibitor, with core of diaryl urea, a new series of derivatives were designed and synthesizedthrough an efficient sequential one-pot reaction and evaluated for their in vitro antiproliferativeactivities against A۵۴۹ and HT-۲۹ cell lines. The most active compound showedanti-proliferative activity in both cells and induced mild apoptosis in HT-۲۹ cells. The resultsof molecular docking simulations showed that the novel compounds bind to VEGFR-۲ in asimilar fashion to that observed for sorafenib.

Keywords:

Diarylurea , Sequential one-pot synthesis , Docking , MTT assay , Apoptosis