Discovery of new quinoxaline-based derivatives as anticancer agents and potent VEGFR-2 inhibitors: Design, synthesis, and in silico study

VEGFR-2 is one of the most vital targets for the treatment of solid tumors. This work represents synthetic approaches of new set of quinoxaline-based derivatives having comparable essential pharmacophoric properties of VEGFR-2 inhibitors. The antiproliferative findings revealed that compound 21a displayed the most potent effect against MCF-7 and HepG2 cell lines with IC50 values of 12.9 and 7.5 mu M, respectively. Further assessment was carried out for all the synthesized members against VEGFR-2 enzyme. Excitingly, the data of VEGFR-2 assay were comparable to that of antiproliferative assay. Compound 21a was the most powerful member against VEGFR-2 with an IC50 value of 3.8 nM, comparing to sorafenib (IC50 = 3.12 nM). Finally, molecular docking experiments were conducted to foresee how the synthesized compounds can bind to their prospective biological target; VEGFR-2. The docking results showed the ability of the synthesized compounds to bind VEGFR-2 in a correct manner. Lastly, computational physicochemical estimation of the most active candidates displayed that they have favorable assets with reasonable drug-likeness reports. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

VEGFR-2 is a crucial target for solid tumor treatment. This study synthesized a series of quinoxaline-based derivatives with comparable pharmacophoric properties to VEGFR-2 inhibitors. The antiproliferative assays showed that compound 21a exhibited the most potent effect against MCF-7 and HepG2 cell lines, and the VEGFR-2 enzyme assays yielded similar results. Molecular docking experiments demonstrated the synthesized compounds' ability to bind to VEGFR-2 correctly. Computational physicochemical estimation indicated that the most active candidates had favorable characteristics and drug-like properties.