Prediction of in silico ADMET Properties and Molecular Docking Study of Substituted Thiadiazole for Screening of Antibacterial and Antifungal Activities against Protein Targets Helicobacter pylori α-Carbonic Anhydrase and Trypanosoma brucei Pteridine Reductase

Abstract

The aim of this work was to evaluate the physico-chemical, pharmacokinetic parameters (absorption, distribution, metabolism, excretion and toxicity) and pharmacodynamic parameters (bioactivity and adverse reactions) of substituted thiadiazole by means of in silico computational prediction. Online softwares such as Pre-ADMET, Molinspiration and rule of five were used for the analysis. Substituted thiadiazole fits the characteristics of drug-likeness, pharmacokinetic properties appropriate to the predicted patterns and activities within the scope for the treatment of infection in the stomach or duodenum (first part of the small intestine), gastritis and trypanosomiasis. Therefore, in silico results allow us to conclude that substituted thiadiazole is predicted to be a potential future drug candidate, due to its relevant Drug-likeness profile, bioavailability, excellent liposolubility and adequate pharmacokinetics, including at the level of CNS, penetrating the blood-brain barrier. Molecular docking studies have also been performed to screen the antibacterial and antifungal activities of the 50 designed compounds against protein targets Helicobacter pylori α-carbonic anhydrase (PDB: 5TUO) and Trypanosoma brucei Pteridine Reductase (PTR1) (PDB: 4WCD) respectively. Among all the compounds C11 exhibited the most significant affinity score against Helicobacter pylori α-carbonic anhydrase and C37 exhibited the most significant affinity score against Trypanosoma brucei pteridine reductase (PTR1) best significant hydrogen bonds interaction at the active site of protein.