Extra precision glide docking, free energy calculation and molecular dynamics studies of 1,2-diarylethane derivatives as potent urease inhibitors

Abstract

For the latter half of the twentieth century, most medical professionals considered bacterial infection to be a primary cause of gastrointestinal ulcers in human beings. In 1994, the World Health Organization (WHO) recognized Helicobacter pylori, the bacterium most closely linked to ulcer development, as a type I carcinogen. Biological research has shown that there is a positive correlation between the number of species in the Helicobacter genus and the number of medical conditions associated with Helicobacter infection, both of which are increasing rapidly. N-Benzylaniline derivatives, frequently used in industrial manufacturing, are being considered as a strong candidate for ongoing drug modeling in search of novel therapies. The basic goal behind this study was to determine the potency of experimentally proved data, and to determine favorable substituents to enhance potency, and thereafter to support this finding through theoretical modification of the existing base skeleton by addition of suitable substituents. Ligands were investigated thoroughly by paying attention to the urease-inhibitory properties present in the selected series. Initially, docking was performed on ligands with protein to produce efficient docking poses. Molecular dynamics (MD) simulations were also performed to precisely understand the interactions between ligands and proteins. Thereafter, MM-GBSA was used in order to validate the methods and results. Good interaction was observed with amino acids Arg338, Ala169, Asp223, His322, and Asn168. This study also revealed that the electron rich hydroxyl group (-OH) substituent plays an important role during bond formation. In addition, various hydrogen bonds, ionic bonds, and pi-pi stacking bonds make significant contributions towards urease inhibition. Therefore, further research utilizing electron-rich moieties may lead to novel and efficacious urease inhibitors.

Molecular modelling of SdiA protein by selected flavonoid and terpenes compounds to attenuate virulence in Klebsiella pneumoniae

“…The good docking scores observed for the tested terpenes and flavonoids imply that they have inhibitory actions that are linked to SdiA binding mechanisms. This also suggests that they may be physiologically active as well as highly efficient molecules, as they provide energy to promote the protein-ligand binding interaction (Gupta & Bajaj, 2018). The direct binding of virulence-associated proteins as observed in this study can be added as potent therapeutic target of flavonoids, in addition to the antibacterial mechanism of action, as also noted by Donadio et al (2021).…”

In Silico and In Vitro Screening of Antipathogenic Properties of Melianthus comosus (Vahl) against Pseudomonas aeruginosa

“…Docking results of the compounds on the LasR receptor also revealed varying glide energy. High binding/glide energy scores of the compounds represents supportive energy for the protein-ligand binding interaction and indicates that they may be biologically active as well as highly efficient compounds [29].…”

“…Four main constituents were identified in M. comosus methanol extract as decane (1), guanosine (4), 1,2-benzene dicarboxylic acid, diethyl ester (6) and neophytadiene (12). The main components detected from dichloromethane extract were heptacosane (29), nonacosane (32) dotriacontane (35) and hexatriacontane (36). The common compounds identified from all three extracts (aqueous, methanol and dichloromethane) were 1,2-benzene dicarboxylic acid, diethyl ester (6) and neophytadiene (12) and hexadecanoic acid (18).…”

Drug screening and identification of key candidate genes and pathways of rheumatoid arthritis

“…in addition, energy minimization was performed on the lilrB1 protein structure. TcM docking and the selection of candidate compounds was performed using the virtual screening workflow model of Schrodinger and Glide XP (extra precision), respectively (31)(32)(33).…”