In Silico Study Comparison of Breast Anticancer Activity of Quercetin Compounds with Quercetin Derivatization of HER-2 Protein

Abstract

HER-2 (Human Epidermal Growth factor receptor-2) plays a role in proliferation, migration, survival and cell growth. Specifically, 20-30% overexpression of HER-2 can lead to the development of breast cancer cells. Compound 03Q (2 - {2-[ 4 - ( { 5 - chloro - 6 - [ 3 - ( trifluoromethyl ) phenoxy ] pyridine - 3 -yl } amino ) - 5H - pyrrolo [3,2 d ] pyrimidine-5-yl ] ethoxy } ethanol), as a native ligand that functions as an HER-2 inhibitor (Carpenter and Lo, 2013). Later, quercetin will be docked and the comparison compound 2',6-diisopropyl quercetin will be tested in silico with molecular docking. Molecular docking in silico is carried out in several stages such as method validation, optimization of the structure of the native ligand compound or its comparison in 3D, and the docking of each compound will be optimized with HER-2 inhibitor protein which refers to the binding energy parameter where the lower the bond energy value, the higher the bond energy. strong and stable bonds that occur between native ligand compounds or comparison compounds with HER-2 inhibitor proteins. Based on the docking results, it is known that 2'6-diisopropylquercetin has a Ki value of 699.02 M. These results indicate that 2'6-diisopropylquercetin has inhibitory activity against HER-2 although the effectiveness of quercetin is five hundred times better (14.78 M). Based on the results of this study, it is known that 2'6-diisopropylquercetin is able to bind to the HER-2 receptor stably and has an inhibitory effect on the receptor although its binding is not as good as that of quercetin