Design and synthesis of 6-amino-quinoxaline-alkynyl as potential aromatase (CYP19A1) inhibitors

Herein we report the design and synthesis of 6-amino-quinoxaline-alkynyl derivatives, which were evaluated for their anti-cancer properties against MCF-7 breast cancer cells. A total 11 amino-quinoxaline compounds were identified by molecular docking from a library of over 100 compounds, to be potential aromatase (CYP19A1) inhibitors. MD simulations shed more light on the equilibration and stabilities of the enzyme-ligand complexes. All identified compounds were synthesised and evaluated against breast cancer (MCF-7), with three compounds 5, 8 and 15 showing promising inhibitory activity against MCF-7 at IC50 of 69.7, 35.6 and 69.8 µM, respectively. Compounds 5 and 8 were also observed to inhibit aromatase CYP19A with IC50 of 12.2 and 66.7 µM, respectively. The nitro-quinoxaline derivatives, which were intermediates in the synthesis of the amino-quinoxaline compounds, were found to be active against Mycobacterium tuberculosis (Mtb) H37Rv strain, with seven compounds; 18, 19, 24, 25, 27, 28 and 29, having MIC90 ranging from 0.6 to 9.5 µM. [Display omitted]