Chemical Constituents from Artemisia annua and Vitex agnus-castus as New Aromatase Inhibitors: In-vitro and In-silico Studies
Abstract. Aromatase inhibitors are important in certain cancers such as breast cancer in postmenopausal women. In this study, eight constituents from Artemisia annua L. and Vitex agnus-castus L. were isolated and evaluated for their aromatase inhibitory activity using in-vitro fluorimetric assay. All tested compounds possessed moderate to strong inhibitory activity with β-sitosterol and myricetin-3,7,4'-trimethyl ether being the most active with IC50 values of 0.13 and 0.25 μM, respectively. Compounds were subjected to induced fit docking (IFD) where β-sitosterol, possessed comparable interaction patterns to the natural co-crystallized ligand androstenedione. Furthermore, Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME&T) properties of the compounds were evaluated revealing that all compounds' properties - except some of β- sitosterol related to solubility - lied within the acceptable range for human use, thereby considered as competent drug-like molecules. These findings could qualify β- sitosterol, myricetin-3,7,4'-trimethyl ether and domesticoside as lead compounds for the development of new aromatase inhibitors.
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