In Silico Analysis of α-Mangostin Derivatives: Investigating Their Interaction with B-cell Lymphoma 2 (Bcl-2) Receptor

α-Mangostin emerges as a highly potent chemopreventive and chemotherapeutic agent, demonstrating significant efficacy in suppressing carcinogenesis at various stages, including cell division, proliferation, apoptosis, inflammation, and metastasis. Furthermore, derivatives of α-Mangostin exhibit potential in addressing cancer-related ailments. This study aimed to investigate the binding interactions and dynamic behavior of α-Mangostin derivatives with the B-cell lymphoma 2 receptor (Bcl-2) through a comprehensive computational approach that combined molecular docking, molecular dynamics simulation, and ADMET prediction. The physicochemical and pharmacokinetic properties of α-Mangostin and its derivatives were predicted using the SWISS-ADME tool and the pkCSM web service, employing SMILES data as input. For molecular docking, the three-dimensional structure of Bcl-2 was utilized, and docking simulations were conducted using the Gnina software to explore the affinity and interaction of the derivatives with Bcl-2. Among the derivatives, derivative 6 displayed the most promising docking results, with a binding energy of -7.95 kcal/mol and significant π-Sigma interaction at the active site on the Tyr161 amino acid residue. Additionally, interactions such as conventional hydrogen bonds, carbon hydrogen bonds, π-cation, and alkyl were observed. To assess the stability and dynamic behavior of derivative 6 in the Bcl-2 complex, a 100-nanosecond molecular dynamics (MD) simulation was performed using GROMACS software. The results suggest that derivative 6 derived from α-Mangostin holds potential for oral drug development, highlighting its promise for future therapeutic applications based free energy calculation using molecular mechanics generalized born surface area (MM-GBSA).