Design, Synthesis, and Molecular Docking Studies of Some New Quinoxaline Derivatives as EGFR Targeting Agents

The synthesis of some new quinoxaline derivatives (IVa–n) and their structure determination using (1)H NMR, (13)C NMR and mass spectral analysis was described herein. The in vitro anti-cancer activity of the these compounds (IVa–n) revealed that the compound1-((1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(tetrazolo[1,5-a]quinoxalin-4-yl)pyrazolidine-3,5-dione (IVd) has shown promising activity, whereas, compounds 1-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-2-(tetrazolo[1,5-a]quinoxalin-4-yl)pyrazolidine-3,5-dione (IVa), 1-(tetrazolo[1,5-a]quinoxalin-4-yl)-2-((1-(m-tolyl)-1H-1,2,3-triazol-4-yl)methyl)pyrazolidine-3,5-dione (IVb), 1-((1-(3,5-dimethoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(tetrazolo[1,5-a]quinoxalin-4-yl)pyrazolidine-3,5-dione (IVh) and 1-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(tetrazolo[1,5-a]quinoxalin-4-yl)pyrazolidine-3,5-dione (IVi) exhibited good to moderate activity against four human cancer cell lines such as HeLa, MCF-7, HEK 293T, and A549 as compared to the doxorubicin. Predominantly, the compound displayed excellent activity over HeLa, MCF-7, HEK 293T, and A549 with IC(50) values of 3.20 ± 1.32, 4.19 ± 1.87, 3.59 ± 1.34, and 5.29 ± 1.34 μM, respectively. Moreover, molecular docking studies of derivatives (IVa–n) on EGFR receptor suggested that the most potent compound strongly binds to protein EGFR (pdbid:4HJO) and the energy calculations of in silico studies were also in good agreement with the obtained IC(50) values. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1134/S1068162022030220.