Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans-sialidase

João Neres; Pascal Bonnet; Philip N Edwards; Pravin L Kotian; Alejandro Buschiazzo; Pedro M Alzari; Richard A Bryce; Kenneth T Douglas

doi:10.1016/j.bmc.2006.12.024

Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans-sialidase

Bioorg Med Chem. 2007 Mar 1;15(5):2106-19. doi: 10.1016/j.bmc.2006.12.024. Epub 2006 Dec 15.

Authors

João Neres¹, Pascal Bonnet, Philip N Edwards, Pravin L Kotian, Alejandro Buschiazzo, Pedro M Alzari, Richard A Bryce, Kenneth T Douglas

Affiliation

¹ School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, M13 9PL, UK.

PMID: 17218104
DOI: 10.1016/j.bmc.2006.12.024

Abstract

Benzoic acid and pyridine derivatives inhibit recombinant trans-sialidase from Trypanosoma cruzi with I50 values between 0.4 and 1mM. The best compounds, 4-acetylamino-3-hydroxymethylbenzoic acid and 5-acetylamino-6-aminopyridine-2-carboxylic acid, provide new leads to inhibitors not containing the synthetically complex sialic acid structure. The weak inhibition by such compounds contrasts with their much stronger inhibition of neuraminidase from Influenza virus.

Publication types

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

MeSH terms

Animals
Benzoic Acid / chemistry
Benzoic Acid / pharmacology*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Glycoproteins / antagonists & inhibitors*
Magnetic Resonance Spectroscopy
Models, Molecular
Neuraminidase / antagonists & inhibitors*
Pyridines / chemistry
Pyridines / pharmacology*
Spectrometry, Mass, Electrospray Ionization
Trypanosoma cruzi / enzymology*

Substances

Enzyme Inhibitors
Glycoproteins
Pyridines
Benzoic Acid
trans-sialidase
Neuraminidase