In silico studies: Physicochemical properties, drug score, toxicity predictions and molecular docking of organosulphur compounds against Diabetes mellitus

• Published in: Journal of molecular recognition 2021-11, Vol.34 (11), p.e2925-n/a
• Main Authors: Rajalakshmi, Ravimoorthy, Lalitha, Pottail, Sharma, Sreenivasa Chandramouli, Rajiv, Asha, Chithambharan, Akhila, Ponnusamy, Aruna
• Format: Article
• Language: English
• Subjects: Acarbose; Aniline; Biocompatibility; Biopharmaceuticals; Cell injury; Computer Simulation; Diabetes; Diabetes mellitus; Diabetes Mellitus - drug therapy; Dipeptidyl Peptidase 4 - chemistry; Dipeptidyl peptidase‐4; Dipeptidyl-Peptidase IV Inhibitors - chemistry; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; Drug Design; Drug Discovery; Drugs; Formulations; Hepatocytes; Hex 6.3; Humans; Hydrocarbons, Aromatic - chemistry; Hydrocarbons, Aromatic - pharmacology; Hypoglycemia; Ligands; Maestro Schrodinger; Mathematical analysis; Metabolic disorders; Metformin; Miglitol; Molecular docking; Molecular Docking Simulation; Molecular Dynamics Simulation; Organosulfur compounds; organosulphur compounds; Peptidase; Peptidases; Pharmaceutical Preparations; Physicochemical properties; Predictions; Side effects; Solubility; Sulfhydryl Compounds - chemistry; Sulfhydryl Compounds - pharmacology; Sulfur; Sulfur compounds; Thiazolidinediones; Toxicity; Toxicity Tests; Urea
• ISSN: 0952-3499; 1099-1352
• DOI: 10.1002/jmr.2925

Diabetes mellitus (DM) is a significant common metabolic disorder seen all over the world. In 2020, according to the International Diabetes Federation (IDF), out of 463 million people who have diabetes all over the world, 77 million belong to India. As per the statistical prediction, the affected numbers are probably expected to rise to 642 million by 2040. The commercially available anti‐diabetic drugs in the market include metformin, sulphonyl urea, meglitinides, miglitol, acarbose, biguanides, and thiazolidinediones cause side effects like hypoglycaemia, dizziness, liver cell injury, digestive discomfort, neurological defects, etc. Hence, bioactive organosulphur based functional ligands are chosen in this study to arrive at a newer drug for DM. In this work, in silico analysis of organosulphur molecular descriptors like physicochemical properties, solubility, drug score, and toxicity predictions are evaluated using OSIRIS and Toxtree freeware. The essential parameters for discovering drugs for biopharmaceutical formulations viz the solubility of drugs and toxicity have been calculated. The protein target Dipeptidyl peptidase DPP4 (PID: 2RIP) was docked against energy minimised sulphur compounds using Hex 6.3. The results indicate that the drug likeliness of the molecule 4, that is, N‐[(3,3‐dimethyl piperidin‐2‐yl) methyl]‐4‐ethyl sulphonyl aniline is active with decreasing binding energy score (−212.24 Kcal mol−1) with no toxicity and also few sulphur compounds are active against diabetes compared to standard drug metformin (−158.33 Kcal mol−1). The best drug‐like ligand N‐[(3,3‐dimethyl piperidin‐2‐yl) methyl]‐4‐ethyl sulphonyl aniline, was docked using commercial Maestro Schrodinger software to predict the results. The current study focuses on in silico analysis of bioactive organosulphur compounds for their potent antidiabetic activity. The physicochemical properties, drug score and toxicity, have been evaluated using Marvin, OSIRIS and Toxtree. Out of the 34 sulphur‐based ligands, N‐[(3,3‐dimethyl piperidin‐2‐yl) methyl]‐4‐ethyl sulphonyl aniline possesses the best docking energy value against control metformin using Hex 6.3 freeware and commercial GLIDE 9.3 software. Therefore, we conclude that organosulphur based ligand N‐ [(3,3‐dimethyl piperidin‐2‐yl) methyl]‐4‐ethyl sulphonyl aniline could act against Diabetes mellitus.