Design of vonoprazan pyrazole derivatives as potential reversible inhibitors of gastric proton pump: An in silico molecular docking study
Abstract
Despite the fact that proton pump inhibitors are widely used for the inhibition of gastric acid secretion, recent studies have revealed certain long-term side effects. Due to acidic environment in the stomach, it is challenging to design new competitive inhibitors of gastric proton pump with more potent inhibition of gastric acid secretion to conventional drugs. The aim of this in silico study was to assess the potential of designed vonoprazan derivatives to inhibit the gastric proton pump using molecular docking study. The distribution-based design of the vonoprazan derivatives was carried out by optimization of the distribution coefficient at physiological pH and pKa values. A molecular docking study was performed using the protein structure of gastric proton pump (PDB ID: 5YLU) in complex with vonoprazan in AutoDock Vina software. According to the estimated values of docking scores, derivatives 11, 21, and 25 showed the highest binding affinity to gastric proton pump. Compounds 3, 13, 14, 16, 17, 20, 22, and 23 formed the highest number of significant binding interactions with the active site of proton pump. Based on the obtained binding parameters, it can be concluded that derivatives 14 and 23 achieved the highest number of significant binding interactions (16 and 15, respectively) with concomitant lower values of the docking scores (-9.2 and-9.3 kcal/mol) compared to vonoprazan as a binding control. Based on the binding assessment criteria, these two compounds…
How strong is the evidence?
Evidence Hub reads this as a simulation / modelling, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018
- Improving sleep quality leads to better mental health: A meta-analysis of randomised controlled trials
- Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study
- Occupation and risk of severe COVID-19: prospective cohort study of 120,075 UK Biobank participants
- Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study
- Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.