Exploring natural anthraquinones as potential MMP2 inhibitors: A computational study

Objective: Matrix metalloproteinase-2 (MMP2) plays a significant role in cleaving extracellular matrix components, leading to many cancer cells' progression and invasion behavior. Therefore, MMP2 inhibition may hold promise for cancer treatment. Anthraquinones have shown antineoplastic effects, some of which have been used in clinical practice as anticancer drugs. This study used a computational drug discovery approach to assess the possible inhibitory effects of selected anthraquinones on MMP2. The results were then compared with that of Captopril, which was considered a standard drug. Methods: This study used the AutoDock 4.0 tool to evaluate the binding affinity of 21 anthraquinones to the MMP2 catalytic domain. The most favorable scores based on the Gibbs free binding energy scores were given to the highest-ranked ligands. The Discovery Studio Visualizer tool illustrated interactions between MMP2 residues and top-ranked anthraquinones. Results: A total of 12 anthraquinones were identified with Delta Gbinding scores less than - 10 kcal/mol. Pulmatin (Chrysophanol-8-glucoside) was the most potent MMP2 inhibitor, with a Delta Gbinding score of - 12.91 kcal/mol. This anthraquinone was able to restrict MMP2 activity within a picomolar range. Conclusion: MMP2 inhibition by anthraquinones, notably Pulmatin, may be a useful therapeutic approach for cancer treatment.