Podophyllotoxin, Deoxypodophyllotoxin and Ursolic Acid as Potential Inhibitors of tcpA, ompW, and ctxB Genes in Vibrio cholerae: An in-Silico Study

Abstract

Introduction: Cholera is a highly contagious disease that causes severe diarrhea and dehydration. This study investigated podophyllotoxin, deoxypodophyllotoxin, and ursolic acid as inhibitors of tcpA , ompW, and ctxB genes in Vibrio cholerae . Methods: We obtained the crystallized structure of podophyllotoxin, deoxypodophyllotoxin, and ursolic acid from the PubChem database for use as a ligand. The mm 2 method in Chem3D v20.1.1.125 was used to optimize the structure of the ligands. We used AutodackVina v.1.2.0 to evaluate the ligands as inhibitors against the active site of the tcpA , ompW , and ctxB proteins. The output results were analyzed and assessed by BIOVIA Discovery Studio 2016 V16.1.0 X64. Results: The reported affinities ranged from -6.8 and -8.7 kcal/mol. The highest diversity of links was found in tcpA and ctxB . Hydrogen bonds were established with Threonine (91, 111), Glycine (113, 114, 94), and Alanine (92) of tcpA , indicating the effectiveness of ligands against tcpA . The ligands podophyllotoxin, deoxypodophyllotoxin, and ursolic acid showed a variety of hydrogen bonds against ompW and ctxB , respectively, with Arginine, Isoleucine, Histidine, Glycine, and Glutamine. These results demonstrate the excellent inhibitory effects of the ligands against Vibrio cholerae . Conclusion: Vibrio cholerae plays a crucial role in causing pandemic cholera in humans. The predicted conformations of the ligands in this study showed that podophyllotoxin and deoxypodophyllotoxin have higher inhibitory potential than ursolic acid. Therefore, podophyllotoxin and deoxypodophyllotoxin can be potential agents for further research in developing Anti-Vibrio cholerae drugs.