Inhibition of protein glycation by urea and thiourea derivatives of glycine/proline conjugated benzisoxazole analogue - synthesis and structure-activity studies

C S Shantharam; D M Suyoga Vardhan; R Suhas; M B Sridhara; D Channe Gowda

doi:10.1016/j.ejmech.2012.12.029

Inhibition of protein glycation by urea and thiourea derivatives of glycine/proline conjugated benzisoxazole analogue - synthesis and structure-activity studies

Eur J Med Chem. 2013 Feb:60:325-32. doi: 10.1016/j.ejmech.2012.12.029. Epub 2012 Dec 20.

Authors

C S Shantharam¹, D M Suyoga Vardhan, R Suhas, M B Sridhara, D Channe Gowda

Affiliation

¹ Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore - 570 006, Karnataka, India.

PMID: 23314045
DOI: 10.1016/j.ejmech.2012.12.029

Abstract

Synthesis of a new series of urea/thiourea derivatives of Gly/Pro conjugated benzisoxazole has been reported. Structure of the compounds was characterized by physical and spectroscopical data and has been screened for their in vitro antiglycation activity. Several compounds showed promising activity with IC(50) < 5 μM compared to standard rutin (IC(50) = 41.9 μM). Further, it was found that compounds containing methoxy and bromine substituents have exerted highly potent activity. Thus, the title compounds represent novel class of potent antiglycating agents.

MeSH terms

Animals
Cattle
Dose-Response Relationship, Drug
Glycine / chemistry*
Isoxazoles / chemistry*
Molecular Structure
Proline / chemistry*
Serum Albumin, Bovine / antagonists & inhibitors*
Serum Albumin, Bovine / metabolism
Structure-Activity Relationship
Urea / analogs & derivatives
Urea / chemistry
Urea / pharmacology*

Substances

1,2-benzisoxazole
Isoxazoles
Serum Albumin, Bovine
Urea
Proline
Glycine