Bromotyrosine-derived natural and synthetic products as inhibitors of mycothiol-S-conjugate amidase

Gillian M Nicholas; Lisa L Eckman; Satyajit Ray; Robert O Hughes; Jeffrey A Pfefferkorn; Sofia Barluenga; K C Nicolaou; Carole A Bewley

doi:10.1016/s0960-894x(02)00385-2

Bromotyrosine-derived natural and synthetic products as inhibitors of mycothiol-S-conjugate amidase

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2487-90. doi: 10.1016/s0960-894x(02)00385-2.

Authors

Gillian M Nicholas¹, Lisa L Eckman, Satyajit Ray, Robert O Hughes, Jeffrey A Pfefferkorn, Sofia Barluenga, K C Nicolaou, Carole A Bewley

Affiliation

¹ Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0820, USA.

PMID: 12161164
DOI: 10.1016/s0960-894x(02)00385-2

Abstract

A series of bromotyrosine-derived compounds, including marine natural products and members of a psammaplin A-inspired combinatorial synthetic library, were screened for their ability to inhibit the Mycobacterium tuberculosis detoxification enzyme mycothiol-S-conjugate amidase (MCA). Correlations between the structures and their respective IC(50) values (which range from 3 microM to 2.7 mM) should prove valuable when optimizing more potent inhibitors of MCA.

Publication types

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

MeSH terms

Amidohydrolases / antagonists & inhibitors*
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / pharmacology
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Inhibitory Concentration 50
Mycobacterium tuberculosis / enzymology
Structure-Activity Relationship
Tyrosine / analogs & derivatives
Tyrosine / chemistry
Tyrosine / pharmacology

Substances

Anti-Bacterial Agents
Enzyme Inhibitors
bromotyrosine
Tyrosine
Amidohydrolases
mycothiol S-conjugate amidase