Design, synthesis and biological characterization of thiazolidin-4-one derivatives as promising inhibitors of Toxoplasma gondii

Eur J Med Chem. 2014 Aug 15;86C:17-30. doi: 10.1016/j.ejmech.2014.08.046. [Epub ahead of print]

 

D'Ascenzio M¹, Bizzarri B², De Monte C¹, Carradori S¹, Bolasco A¹, Secci D¹, Rivanera D³, Faulhaber N⁴, Bordón C⁴, Jones-Brando L⁴.

 

We designed and synthesized a large number of novel thiazolidin-4-one derivatives for the evaluation of their anti-Toxoplasma gondii activity. This scaffold was functionalized at the N1-hydrazine portion with aliphatic, cycloaliphatic and (hetero)aromatic moieties. Then, a benzyl pendant was introduced at the lactamic NH of the core nucleus to evaluate the influence of this chemical modification on biological activity. The compounds were subjected to several in vitro assays to assess their anti-parasitic efficacy, cytotoxicity on fibroblasts, inhibition of tachyzoite invasion/attachment and replication after treatment. Results showed that fourteen of these thiazole-based compounds compare favorably to control compound trimethoprim in terms of parasite growth inhibition.
Copyright © 2014. Published by Elsevier Masson SAS.

KEYWORDS:

Cytotoxicity; Host cell invasion; Parasite growth inhibition; Thiazolidin-4-one; Toxoplasma

PMID:

25140751

[PubMed - as supplied by publisher]