Silvi Zakiyatul Ilmiyah, Sofy Permana, Edwin Widodo, Eviana Norahmawati, Happy Kurnia Permatasari, Yoshiyuki Kawamoto, Nik Ahmad Nizam Nik Malek, Agustina Tri Endharti
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. © 2025 Journal of Pharmacy & Pharmacognosy Research.
Doctoral Program in Medical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Biology, Faculty of Mathematic and Natural Sciences, Universitas Brawijaya, Malang, Indonesia; Department of Physiology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Anatomical Pathology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Biochemistry and Biomolecular, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Biomedical Sciences, Graduate School of Life and Health Sciences, Chubu University, Japan; Centre for Sustainable Nanomaterials (CSNano), Universiti Teknologi, Malaysia; Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Biomedical Central Laboratory, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
