Decoding the multifunctional potential of ursolic acid: antioxidant, antiproliferative, molecular dynamics, and...

Excoecaria agallocha L, a mangrove plant widely used in traditional medication in India, was the focus of this study to evaluate its antioxidant, anticancer, structural, dynamic, and biodegradability properties of its bioactive compound, ursolic acid. This study, a sample (E. agallocha) collected from the tropical Islands ecosystem of South Andaman, India, represents the first report identifying Ursolic acid from the methanolic extract. The structure elucidation of the isolated bioactive compound was characterized using FT-IR, ¹H(Proton), ¹³C(Carbon) NMR spectroscopy, and HRMS. The antioxidant and anticancer activities were evaluated using the DPPH and MTT assay methods, respectively. The methanolic extract of E. agallocha demonstratedsignificantin vitro anticancer activity against Cervical (HeLa) and Breast (MDA-MB231) human cancer cell lines, with notable IC₅₀ values of 19.50 ± 0.41 µg/mL and 20.67 ± 0.14 µg/mL, respectively. It is highlighted that the ursolic acid's anticancer activity was more potent, with IC₅₀ values of 3.5714 µg/mL against MDA-MB231 cells compared to the methanolic extract. The methanolic extract's antioxidant properties with IC₅₀ values of 90.37 ± 0.41 and purified ursolic acid molecule exhibited promising IC₅₀ values of 7.59 ± 0.41 µg/mL. Gas Chromatography-Mass Spectrometry analysis of the methanolic extracts of E. agallocha revealed the presence of numerous pharmacologically bioactive compounds. In the in silico studies, molecular docking of two ligands, Ursolic acid and Obatoclax, with the Bcl-B protein demonstrated notable binding affinities, with ΔG values of -5.8 kcal/mol and - 6.6 kcal/mol, respectively. Ursolic acid's binding affinity is comparable to Obatoclax's, highlighting its potential as a viable anticancerous candidate for targeting Bcl-B protein. Assess the ligands' impact on the protein's stability, flexibility, compactness, folding properties, and solvent accessibility, MD simulations were performed. The MD simulation results revealed that the ligand-bound Bcl-B complexes exhibited significant structural stability, with moderate ligand-induced conformational changes observed in the target protein. Further, BIOWIN™ models indicated that the identified Ursolic Acid is biodegradable in an aerobic environment, underscoring its environmental compatibility. Deciphering the bioactivities of ursolic acid could uncover new therapeutic agents and enhance our understanding of its biodegradable environmental compatibility, revealing the source of already documented pharmacological compounds.