Mangosuthu University of Technology (MUT)
Gumede, Design and synthesis of 6-amino-quinoxaline-alkynyl as potential.pdf (3.01 MB)

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

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journal contribution
posted on 2023-02-21, 10:05 authored by Karabo Lekgau, Lerato A. Raphoko, Charity M. Lebepe, Dikgale F. Mongokoana, Tlabo C. Leboho, Thabe M. Matsebatlela, Njabulo J. Gumede, Winston Nxumalo

Herein we report the design and synthesis of 6-amino-quinoxaline-alkynyl derivatives, which were eval?uated 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 aro?matase 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 My?cobacterium 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. 


University of Limpopo (UL); National Research Foundation (South Africa); Sasol Inzalo Foundation.