Cytotoxic effects of butyric acid derivatives through GPR109A receptor in Colorectal Carcinoma cells by in silico and in vitro methods

Abstract

• The predicted 3D structure of GPR109A showed ideal stereochemical features. • Indole-3-butyrate and tributyrin showed best binding to GPR109A than other derivatives. • The percentage cytotoxicity of ten possible combinations showed concurrent results. • The study suggests the scope of butyric acid derivatives as future leads to cancer. Butyric acid plays an important role in the prevention of colon cancer. Based on the functional role, the GPR109A receptor can be considered as one of the major drug targets for colorectal cancer. The objective of this study was to explore the anti-cancer potential of butyric acid derivatives by analyzing the interaction with the GPR109A receptor and their in vitro studies on HCT116 (Human Colorectal Carcinoma Cell lines) cell lines. Sodium butyrate, Indole-3-butyric acid, Tributyrin, and 2-Amino-n-butyric acid are the derivatives used in the study, and Nicotinate is used as the usual ligand for the GPR109A receptor. The three-dimensional structure of the GPR109A receptor was predicted by homology modeling and the binding affinity of butyric acid derivatives was screened by molecular docking. The percentage of cytotoxicity of ten possible combinations of compounds (5mM each) was analyzed in vitro . The docking studies revealed that Indole-3-butyric acid and Tributyrin are the best ligands against the GPR109A receptor with binding energy, 6.5 kcal/mol and -6.4 kcal/mol, respectively. Thus, this investigation explores the therapeutic possibilities of butyric acid derivatives as probable drug targets for the treatment of colorectal cancer.