Exploring anti-cancer potential of Anredera cordifolia (Ten.) Steenis leaf compounds against MMP-2 receptor in breast cancer: An in silico approach

Context: Breast cancer is characterized by the abnormal growth of cells in the ducts and lobules of the breast. Numerous therapeutic targets for breast cancer are currently under investigation, one of which is matrix metalloproteinase-2 (MMP-2), a heterodimeric protein highly expressed in circulating tumor cells from patients with pancreatic carcinoma, positioning it as a potential target for breast cancer therapy. Anredera cordifolia is a plant known for its medicinal properties with anti-cancer effects, particularly in breast cancer. Aims: To determine the potential of compounds derived from A. cordifolia leaves as drug candidates, specifically focusing on their binding affinity to inhibit the metastasis pathway of MMP-2 protein in breast cancer. Methods: A. cordifolia leaf extraction and LC-MS analysis compound screening, ligand preparation, ADMET analysis, protein pathway network interaction analysis, molecular docking, and molecular dynamics simulations were performed. Results: LC-MS results showed six compounds in A. cordifolia that exhibited the highest mass spectrum values. These were vitexin, saponin, betalain, bethanidine, terpenoid, and ursolic acid. The six compounds were docked with the MMP-2 protein. The highest binding affinities were observed for saponin (-10 kcal/mol), ursolic acid (-9.1 kcal/mol), and vitexin (-8.8 kcal/mol). The molecular dynamics simulations demonstrated that all compounds exhibited stable interactions, with average RMSD values ranging from 1-3 Å. Conclusions: The binding affinity values, binding site similarity of some amino acid residues with the control, and molecular dynamics results for the ligand from A. cordifolia showed stable binding to the MMP-2 protein with a low level of fluctuation.