In Silico Evaluation of Alpha Mangostin and its Derivatives as a potential Anti-Cancer Agents

Alpha-Mangostin, a natural xanthone from Garcinia mangostana , and its structurally optimized derivatives were evaluated as anticancer agents targeting estrogen receptor proteins linked to breast cancer: Estrogen Receptor Alpha(3ERT), Estrogen Receptor Bound to Estradiol(1ERE), and Estrogen Alpha Ligand-Binding Domain Complex(1A52). Alpha-Mangostin functional groups were modified, and derivatives were optimized and ADME properties assessed to predict the pharmacokinetics and drug-likeness. Molecular docking studies disclosed strong binding affinities of the derivatives at the active sites of the target protein, some of which manifested superior stability and higher affinity than the parent compound. Pharmacophore modeling had identified the critical molecular features as supporting these derivatives as highly promising lead compounds for further development of drugs targeting estrogen receptor pathways in breast cancer.