MOLECULAR DOCKING STUDY AS THERAPEUTIC APPROACH FOR TARGETING CHOLECYSTOKININ IN PANCREATIC CANCER

Abstract

Objective: The Cholecystokinin A receptor (CCK-ARs), also known as CCK1 receptor, is a type of G protein-coupled receptor that is primarily responsive to the hormone Cholecystokinin (CCK). CCK-ARs is one of the receptors characterized and validated to promote pancreatic cancer progression. Devazepide is a selective antagonist of the CCK-ARs. This study aims to find a potential ligand that has the most effective and representative interaction with cancer receptors, becoming a new therapeutic effect using molecular docking Molecular Operating Environment (MOE) with receptor code 7F8U. Methods: We conducted an in silico study by docking candidate ligands with Cholecystokinin Receptor (CCKRs) using the MOE 2015 V.10 application. The ligands of choice come from natural ingredients such as curcumin, resveratrol, berberine, baicalein, dioscin, wogonin, and piperine. Validate the receptor with the Root mean Square Deviation (RMSD) value and docking results with the GIBBS S value. Results: 6 compounds, such as curcumin, resveratrol, berberine, baicalein, wogonin, and piperine, were selected for docking as candidates to determine whether they have interactions with CCK-ARs. Based on the docking results, the Gibbs values ​​obtained were -14.9522;-12.4566;-15.5033;-12.6961;-13.4234;-11,6130 joules/kg. mol, berberine is the compound with the lowest Gibbs energy, namely -15.5033 joules/kg. mol and is one of the strongest. The interactions that occur include Methionine A121-side chain donor, Methionine B121-side chain donor, asparagine A333-amine group and nitrogen atom, B333-amine group and nitrogen atom, Arginine A336-negative oxygen atom, and B336-negative oxygen atom. Conclusion: Berberine which is a natural alkaloid, is suitable for devazepide, which is a positive control for ligand interactions when tethered to the CCKRs. This finding could be a potential new drug for pancreatic cancer. However, further studies, such as in vitro, in vivo, and clinical trials need to be conducted for ordering activity, safety, and safety of new drugs.