Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 63, Issue 1, Pages 146-150Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkn451
Keywords
-
Funding
- National Institutes of Health [AI 34885]
- Stanley Medical Research Institute
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R37AI034885, R01AI034885] Funding Source: NIH RePORTER
Ask authors/readers for more resources
We sought to improve upon the usefulness of artemisinins as anti-Toxoplasma agents by synthesizing new unsaturated, carba derivatives and then testing them for in vitro efficacy against three steps of the lytic cycle of Toxoplasma gondii tachyzoites. Novel derivatives of ART were synthesized and then tested for in vitro antiparasitic activity using T. gondii tachyzoites constitutively expressing beta-galactosidase and human fibroblast host cells. Compounds were evaluated for parasite growth inhibition and cytotoxicity, inhibition of replication and inhibition of parasite invasion of host cells. Five of the seven new derivatives, 3a-c, 3e and 3f, effectively inhibited T. gondii growth (IC50 = 1.0-4.4 mu M); however, only three of these proved to be relatively non-cytotoxic (TD50 >= 200 mu M). The same five derivatives also inhibited tachyzoite replication, and attachment to and invasion of host cells as effectively as or better than the parent compound ART. In addition, one of the derivatives incapable of inhibiting growth, deoxy-3a, was found to inhibit parasite invasion. These new artemisinin derivatives have the ability to inhibit multiple steps of T. gondii's lytic cycle. Synthetic unsaturated, carba derivatives of ART have potential as therapeutic agents for the prevention and treatment of toxoplasmosis in humans.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available