MOLECULAR MODELING STUDIES OF N, N -DISUBSTITUTED DERIVATIVES AS POTENT UREASE INHIBITORS

Abstract

The discovery of Helicobacter pylori in the human stomach by Professor W. Jaworski has encouraged many scientists to study these bacteria, their characteristics, and their effect on human health. In 1982, Marshall and Warren showed experimentally that H. pylori infection is responsible for human gastritis. The pathogenic urease found in H. pylori causes infection not only in the stomach, but also in the duodenum, uterus, and urinary tract, among others. To determine the efficacy and potency of newly synthesized compounds in treating H. pylori infection, docking studies were performed with the 1E9y protein. During these studies, the Arg338, Ala365, Asn168, and Hie221 amino acids were observed to actively participate in bond formation with the studied compounds. In this series of compounds, only the R2 –substituted group is responsible for the observed biological activity. In this study, the results have been revaluated with MD simulations, in which the potency of the compounds was assessed by the percent contribution of hydrogen bonds at the end of the simulation. To calculate the free energy, the present study employs MMGBSA and finds the deviation of the RMSD value.