Chemical Constituents from Artemisia annua and Vitex agnus-castus as New Aromatase Inhibitors: In-vitro and In-silico Studies

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 βsitosterol related to solubility lied within the acceptable range for human use, thereby considered as competent drug-like molecules. These findings could qualify βsitosterol, myricetin-3,7,4'-trimethyl ether and domesticoside as lead compounds for the development of new aromatase inhibitors.