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

João Neres (1) , Pascal Bonnet (1) , Philip N Edwards (1) , Pravin L Kotian (2) , Alejandro Buschiazzo (3) , Pedro Alzari (3) , Richard A Bryce (1) , Kenneth T Douglas (1)

1 University of Manchester [Manchester]
2 BioCryst Pharmaceuticals
3 Biochimie Structurale

Benzoic acid and pyridine derivatives inhibit recombinant trans-sialidase from Trypanosoma cruzi with I 50 values between 0.4 and 1 mM. 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.

Domains: Biochemistry [q-bio.BM]; Biochemistry, Molecular Biology

João Neres, Pascal Bonnet, Philip N Edwards, Pravin L Kotian, Alejandro Buschiazzo, et al.. Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans-sialidase. Bioorganic and Medicinal Chemistry, 2007, 15 (5), pp.2106-2119. ⟨10.1016/j.bmc.2006.12.024⟩. ⟨pasteur-02554109⟩