New PPARgamma ligands based on 2-hydroxy-1,4-naphthoquinone: computer-aided design, synthesis, and receptor-binding studies

Sandeep Sundriyal; Bhoomi Viswanad; Elumalai Bharathy; Poduri Ramarao; Asit K Chakraborti; Prasad V Bharatam

doi:10.1016/j.bmcl.2008.04.072

New PPARgamma ligands based on 2-hydroxy-1,4-naphthoquinone: computer-aided design, synthesis, and receptor-binding studies

Bioorg Med Chem Lett. 2008 Jun 1;18(11):3192-5. doi: 10.1016/j.bmcl.2008.04.072. Epub 2008 May 1.

Authors

Sandeep Sundriyal¹, Bhoomi Viswanad, Elumalai Bharathy, Poduri Ramarao, Asit K Chakraborti, Prasad V Bharatam

Affiliation

¹ Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.

PMID: 18482837
DOI: 10.1016/j.bmcl.2008.04.072

Abstract

FlexX-based molecular docking study was employed to identify 2-hydroxy-1,4-naphthoquinone as a new 'acidic head group' for the design of a novel series of PPARgamma ligands. To provide the proof of concept, designed molecules were synthesized and evaluated in a standard radioligand-binding assay. Out of eight molecules, four were found to bind to the murine PPARgamma with IC(50) ranging from 0.2 to 56.2 microM as compared to standard pioglitazone, with IC(50) of 0.7 microM.

Publication types

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

MeSH terms

Animals
Combinatorial Chemistry Techniques
Computer-Aided Design
Drug Design*
Ligands
Mice
Molecular Structure
Naphthoquinones / chemical synthesis*
Naphthoquinones / chemistry
Naphthoquinones / pharmacology*
PPAR gamma / agonists*
Pioglitazone
Protein Binding
Structure-Activity Relationship
Thiazolidinediones / pharmacokinetics

Substances

Ligands
Naphthoquinones
PPAR gamma
Thiazolidinediones
Pioglitazone