Design, synthesis, and anti-proliferative evaluation of new quinazolin-4(3H)-ones as potential VEGFR-2 inhibitors. (1st January 2021)

• Record Type: Journal Article
• Authors: El-Adl, Khaled; El-Helby, Abdel-Ghany A.; Ayyad, Rezk R.; Mahdy, Hazem A.; Khalifa, Mohamed M.; Elnagar, Hamdy A.; Mehany, Ahmed B.M.; Metwaly, Ahmed M.; Elhendawy, Mostafa A.; Radwan, Mohamed M.; ElSohly, Mahmoud A.; Eissa, Ibrahim H.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 29(2021)
• Publication Date: 2021-01-01
• Subjects: Anticancer -- Molecular docking -- Quinazolin-4(3H)-one -- VEGFR-2; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2020.115872
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: Nineteen compounds of novel quinazolin-4(3 H )-one derivatives were designed and synthesized. Cytotoxic activities were evaluated against HepG-2, MCF-7 and HCT-116 cell lines. In vitro anti VEGFR-2 activities were evaluated. Molecular docking studies were carried out. Abstract: Inhibiting VEGFR-2 has been set up as a therapeutic strategy for treatment of cancer. Thus, nineteen new quinazoline-4(3 H )-one derivatives were designed and synthesized. Preliminary cytotoxicity studies of the synthesized compounds were evaluated against three human cancer cell lines (HepG-2, MCF-7 and HCT-116) using MTT assay method. Doxorubicin and sorafenib were used as positive controls. Five compounds were found to have promising cytotoxic activities against all cell lines. Compound 16f, containing a 2-chloro-5-nitrophenyl group, has emerged as the most active member. It was approximately 4.39-, 5.73- and 1.96-fold more active than doxorubicin and 3.88-, 5.59- and 1.84-fold more active than sorafenib against HepG2, HCT-116 and MCF-7 cells, respectively. The most active cytotoxic agents were further evaluated in vitro for their VEGFR-2 inhibitory activities. The results of in vitro VEGFR-2 inhibition were consistent with that of the cytotoxicity data. Molecular docking of these compounds into the kinase domain, moreover, supported the results.