2'-Hydroxy flavanone derivatives as an inhibitors of pro-inflammatory mediators: Experimental and molecular docking studies

Neeraj K Patel; Khemraj Bairwa; Rahul Gangwal; Gaurav Jaiswal; Sanjay M Jachak; Abhay T Sangamwar; Kamlesh K Bhutani

doi:10.1016/j.bmcl.2015.03.025

2'-Hydroxy flavanone derivatives as an inhibitors of pro-inflammatory mediators: Experimental and molecular docking studies

Bioorg Med Chem Lett. 2015 May 1;25(9):1952-5. doi: 10.1016/j.bmcl.2015.03.025. Epub 2015 Mar 14.

Authors

Neeraj K Patel¹, Khemraj Bairwa¹, Rahul Gangwal², Gaurav Jaiswal¹, Sanjay M Jachak¹, Abhay T Sangamwar², Kamlesh K Bhutani³

Affiliations

¹ Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160 062, India.
² Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160 062, India.
³ Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160 062, India. Electronic address: kkbhutani@niper.ac.in.

PMID: 25824662
DOI: 10.1016/j.bmcl.2015.03.025

Abstract

2'-Hydroxy flavanone (1) was previously isolated from Mimosa pudica (L.) whole plant and was found to exhibit anti-inflammatory effects in vitro. There are also reports on anti-inflammatory properties of compounds bearing flavanone/chromone nucleus. Taking this into account, fourteen derivatives of 2'-hydroxy flavanone (1) were synthesized and evaluated against pro-inflammatory mediators (TNF-α, IL-1β and NO) in in vitro and in vivo models. Results directed that among the synthesized compounds, four derivatives (11-14) showed profound inhibition of pro-inflammatory mediators as compared to the lead molecule. Further, 11-14 demonstrated comparable anti-inflammatory activity with ibuprofen in carrageenan-induced rat paw edema assay and appreciable inhibition of lipopolysaccharide (LPS) induced pro-inflammatory mediators (TNF-α and IL-1β) in Sprague Dawley (SD) rats. The synthesized compounds were further subjected to molecular docking analysis and in silico prediction of pharmacokinetic properties.

Keywords: 2′-Hydroxy flavanone; Anti-inflammatory activity; Flavanones; Interleukin 1β; Nitric oxide; Tumor necrosis factor-α.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Survival / drug effects
Dose-Response Relationship, Drug
Edema / drug therapy
Flavanones / chemistry
Flavanones / isolation & purification
Flavanones / pharmacology*
Inflammation / drug therapy
Interleukin-1alpha / antagonists & inhibitors*
Interleukin-1alpha / metabolism
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Mice
Mimosa / chemistry*
Molecular Docking Simulation*
Molecular Structure
Nitric Oxide / antagonists & inhibitors*
Nitric Oxide / biosynthesis
Plant Extracts / chemistry
Plant Extracts / isolation & purification
Plant Extracts / pharmacology*
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Tumor Necrosis Factor-alpha / metabolism

Substances

2'-hydroxyflavanone
Flavanones
Interleukin-1alpha
Lipopolysaccharides
Plant Extracts
Tumor Necrosis Factor-alpha
Nitric Oxide