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

Fereshteh Azimian¹ Maryam Hamzeh-Mivehroud² Javid Shahbazi Mojarrad³ Salar Hemmati⁴ Siavoush Dastmalchi⁵

1) Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences
2) Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences
3) Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences
4) Drug Applied Research Center, Tabriz University of Medical Sciences
5) Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences

IOI Code : XBGE-FFZKC
Publication : 11th International Conference on New Solutions in Engineering, Information Science and Technology of the Century ahead(icietconf.com)
Abstract :
    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 diarylurea scaffold has been used widely to design potential anticancer agents due to its important role in angiogenesis which regulates by many growth factors such as the vascular endothelial growth factors (VEGFs) and receptor (VEGFR-2). In order to optimization of sorafenib ,a VEGFR2 inhibitor, with core of diaryl urea, a new series of derivatives were designed and synthesized through an efficient sequential one-pot reaction and evaluated for their in vitro anti-proliferative activities against A549 and HT-29 cell lines. The most active compound showed anti-proliferative activity in both cells and induced mild apoptosis in HT-29 cells. The results of molecular docking simulations showed that the novel compounds bind to VEGFR-2 in a similar fashion to that observed for sorafenib.

Keywords : diarylurea sequential one pot synthesis docking mtt assay apoptosis