Design, synthesis and structure-activity relationships of new phosphinate inhibitors of MurD

Katja Strancar; Didier Blanot; Stanislav Gobec

doi:10.1016/j.bmcl.2005.09.086

Design, synthesis and structure-activity relationships of new phosphinate inhibitors of MurD

Bioorg Med Chem Lett. 2006 Jan 15;16(2):343-8. doi: 10.1016/j.bmcl.2005.09.086. Epub 2005 Nov 3.

Authors

Katja Strancar¹, Didier Blanot, Stanislav Gobec

Affiliation

¹ University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia.

PMID: 16271472
DOI: 10.1016/j.bmcl.2005.09.086

Abstract

A series of new phosphinate compounds were designed and synthesized as inhibitors of the d-glutamic acid-adding enzyme (MurD) involved in peptidoglycan biosynthesis. They were tested against the MurD enzyme from Escherichia coli, allowing initial structure-activity relationships to be deduced. Two compounds had IC(50) values near 100 microM and constitute a promising starting point for further development.

Publication types

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

MeSH terms

Bacterial Proteins / antagonists & inhibitors*
Bacterial Proteins / metabolism
Drug Design
Enzyme Inhibitors* / chemical synthesis
Enzyme Inhibitors* / chemistry
Enzyme Inhibitors* / pharmacology
Escherichia coli / enzymology
Molecular Structure
Peptide Synthases / antagonists & inhibitors*
Peptide Synthases / metabolism
Peptidoglycan / biosynthesis
Peptidoglycan / drug effects
Phosphinic Acids* / chemical synthesis
Phosphinic Acids* / chemistry
Phosphinic Acids* / pharmacology
Stereoisomerism
Structure-Activity Relationship

Substances

Bacterial Proteins
Enzyme Inhibitors
Peptidoglycan
Phosphinic Acids
Peptide Synthases
UDP-N-acetylmuramoylalanine-D-glutamate ligase