In silico Structure-Based Screening of Novel Isatin Containing 1, 3-Oxazine Derivatives as Anti-Thrombin Agents

Abstract

Abstract

Cerebral stroke and Arterial thromboembolic diseases such as ischemic stroke, myocardial infarction, angina pectoris, and other cardiovascular diseases due to thrombosis in developing countries are a leading problem, and are responsible for significant morbidity and mortality [1]. Thrombin is an important target to mimic thrombosis-related diseases by blocking its activity during the blood clotting process [2]. This present work is based on the in silico structure-based screening of isatin containing 1,3-Oxazine analogs as thrombin inhibitors. All the proposed isatin containing 1,3-Oxazines were screened against thrombin target (1KTS) through the in silico process using Autodock Vina [3] software. These Oxazines were further evaluated for ADME, drug-likeness, and Toxicity properties using online tools like Swiss ADME [4] and Chem-Bio Server [5]. A Molecular Dynamics Simulation study was performed using Gromos96 43a1 force field in Gromacs on the best ligand-target complex of compound code: S1. The in silico docking study against Thrombin enzyme (1KTS) using Autodock Vina [3], shown that all the selected ligands has greater or similar activities as compared to the standard thrombin inhibitor (Dabigatran). ADME screening through SwissADME [4] and Toxicity prediction through Chem-Bio Server [5] shows each ligand are safe enough for drug designing purpose and wet-lab studies. Molecular Dynamics Simulation study shows that ligand attained the stability very quickly and also stable up to 20 ns simulation periods. The in silico based screening of 1,3-Oxazine analogs as thrombin inhibitors shows good binding and ADMET properties as compared to the standard (Dabigatran). Molecular Dynamics Simulation study also supports the results of in silico screening process.