Title

Toxoplasma gondii: Inhibitory Activity and Encystation Effect of Securinine and Pyrrolidine Derivatives on Toxoplasma Growth.

Document Type

Article

Publication Date

2-2011

Publication Title

Exp Parasitol

Volume

127

Issue

2

First Page

370

Last Page

375

DOI

10.1016/j.exppara.2010.09.002

Keywords

Toxoplasma gondii, Securinine, Growth inhibition, Differentiation

Abstract

Securinine, an alkaloid originally isolated from Securinega suffruticosa, exhibits a wide range of biological activities, including anti-malarial activity. Along with securinine, 10 pyrrolidine derivatives, generated via the retrosynthesis of (-)-securinine, were selected and tested for their inhibitory activity against Toxoplasma gondii growth in vitro. Anti-Toxoplasma activity correlated to hydrophobicity of the tested compounds. Three pyrrolidine derivatives along with securinine inhibit Toxoplasma proliferation at the micromolar range. These compounds act on parasite proliferation in different capacities, either by slowing the growth rate or inhibiting invasion of host cells. Securinine induces bradyzoite differentiation at comparable levels to treatment with alkali media in vitro.

Comments

We would like to thank Ms. Sirin Chaker and Mr. Vaso Globarevic for technical assistance.

Funding: This work was supported by the Natural Sciences and Engineering Research Council of Canada.