Screening & Identification of aromatase inhibitors from natural sources towards therapeutic management of breast cancer using computational simulations

Breast cancer, which is increasing at high rates every year, has become a serious concern. For breast cancer management, aromatase, which is responsible for estrogen synthesis, and its inhibition are one of the therapeutic approaches. Anastrozole, exemestane, and letrozole are the currently available aromatase inhibitors, but the search for effective natural alternatives continues. This study aims to screen structurally similar analogs of currently available clinical aromatase inhibitors to identify natural compounds, assess their potential aromatase inhibitory effects, and determine their ADME-Tox properties, drug likeness, and interaction profiles. We have retrieved structurally similar analogs of currently available market drugs from PubChem and then natural ones were selected. Further, ADME-Tox and Drug Likeness were studied for those natural compounds from ADMETlab 2.0. Natural compounds that pass ADME-Tox and drug likeness were subjected to molecular docking through AutoDock and PyRx to evaluate binding affinity toward aromatase. Candidates providing a high binding affinity score were taken for Molecular Dynamics Simulation(MDS) through GROMACS. Additional analyses—Principal Component Analysis (PCA), Free Energy Landscape (FEL), and MM/PBSA calculations — were performed to further assess interaction stability. Three natural compounds—C1, C2, and C3—are shortlisted which gives strong binding affinity and stable interaction profiles with aromatase. Principal Component Analysis(PCA) studies provide information revealing their most favourable dynamic behaviour, while FEL and MM/PBSA analyses supported their potential inhibitory strength. This research suggest that compounds C1, C2, and C3 has emerge with a promising aromatase inhibitory activity and may serve as potential natural candidates for breast cancer management. Further validation through in vitro and in vivo studies is recommended.