Natural Terpenoids as Potential MMP-7 Inhibitors in Colon Cancer: A Computational Screening Study

Background: Colorectal cancer is the third most frequent cancer globally. Incidence rises with age and has been highest in developed countries, but it is rapidly increasing in many less developed countries and among younger generations in both developed and developing nations. MMP-7 is a key enzyme in the progression of colon cancer, making it a potential therapeutic target.Methods: This study used a computational screening method to determine the efficacy of natural terpenoids as MMP-7 inhibitors. The MMP-7 inhibitor TQI was used as a positive control. A total of 355 natural terpenoid compounds were gathered from literature and public databases. Each compound was obtained in SDF format, converted into 3D structures for molecular docking analyses. PyRx (0.8 version), utilizing the AutoDock Vina docking engine was employed for virtual screening through molecular docking.Results: Three potential candidates, retinol (vitamin A), carnosic acid, and gibberellic acid, were identified as showing strong binding affinities toward MMP-7 compared with the co-crystallized inhibitor TQI. ADMET analysis indicated compound-specific pharmacokinetic and safety profiles: retinol exhibited high predicted oral bioavailability but lower solubility, whereas carnosic acid and gibberellic acid showed more favorable non-toxicity and hERG safety percentiles.Conclusion: These findings highlight the promise of natural terpenoids as novel MMP-7 inhibitors in colon cancer treatment, necessitating further validation and experimental research to determine their efficacy and therapeutic potential.Keywords:Colon cancer, Natural compounds, Terpenoids, Computational analysis