Tangeretin and its Derivatives: An Integrative Bioinformatic Study of Obesity and Related Immunodeficiency

Abstract

Obesity is a complex and major public health concern known to exacerbate many diseases. There are increasing evidences stating the obese people due to adiposity are getting more susceptible to immune deficiency disorders. Tangeretin is a key member of flavonoids reported to have many favourable biological activities. In search of novel leads in ameliorating obesity and related immunodeficiency, the present study is aimed at the in silico evaluation of tangeretin derivatives to assess their biological role. Initially tangeretin derivatives are designed by molecular manipulation approach.Drug likeness and bioactivity score prediction was done using Molinspiration web tool. Swiss ADME prediction and toxicological predictions were performed. In silico Molecular Docking studies were performed by employing a flexible ligand docking approach using Schrodinger on the protein targets namely leptin, Fat mass and obesity associated protein (FTO), Pancreatic lipase, Peroxisome proliferated receptor (PPARɣ) and NADH oxidase. Further the electronic parameters were computed for the best fitted ligands by DFT analysis. The evaluation of results was made based on Glide (Schrodinger) dock score. Out of 18 screened compounds, some of them showed the best docking scores with the targets when compared with the standard (Lovastatin). Particularly the two ligands (L-13 and L-8) showed the best binding score with all five targets. Moreover, DFT analysis carried out for the tangeretin and best fitted ligands (L13 and L8) substantiated the other in silico studies. These findings probably provide excellent lead candidates for the development of therapeutic drugs in combating obesity and related immune deficiency.