Derivatives of a benzoquinone acyl hydrazone with activity against Toxoplasma gondii

Authors

A. G. Sanford, University of Nebraska at Omaha
T. T. Schulze, University of Nebraska at Omaha
L. P. Potluri, University of Nebraska at Omaha
G. F. Watson, University of Nebraska at Omaha
E. B. Darner, University of Nebraska at Omaha
S. J. Zach, University of Nebraska at Omaha
R. M. Hemsley, University of Nebraska at Omaha
A. I. Wallick, University of Nebraska at Omaha
R. C. Warner, University of Nebraska at Omaha
S. A. Charman, Monash University
X. Wang, University of Nebraska Medical Center
J. L. Vennerstrom, University of Nebraska Medical Center
P. H. Davis, University of Nebraska at Omaha

Author ORCID Identifier

G. F. Watson

J.L. Vennerstrom

P.H. Davis

Document Type

Article

Publication Date

11-10-2018

Publication Title

International Journal for Parasitology: Drugs and Drug Resistance

Volume

8

Issue

3

First Page

488

Last Page

492

Abstract

Toxoplasma gondii is an obligate intracellular parasite with global incidence. The acute infection, toxoplasmosis, is treatable but current regimens have poor host tolerance and no cure has been found for latent infections. This work builds upon a previous high throughput screen which identified benzoquinone acyl hydrazone (KG8) as the most promising compound; KG8 displayed potent in vitro activity against T. gondii but only marginal in vivoefficacy in a T. gondii animal model. To define the potential of this new lead compound, we now describe a baseline structure-activity relationship for this chemotype. Several derivatives displayed IC50's comparable to that of the control treatment pyrimethamine with little to no cytotoxicity. The best of these, KGW44 and KGW59, had higher metabolic stability than KG8. In an in vivo T. gondii murine model, KGW59 significantly increased survivorship. This work provides new insights for optimization of this novel chemotype.

Comments

© 2018 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology.

https://doi.org/10.1016/j.ijpddr.2018.11.001

Recommended Citation

Sanford, A. G.; Schulze, T. T.; Potluri, L. P.; Watson, G. F.; Darner, E. B.; Zach, S. J.; Hemsley, R. M.; Wallick, A. I.; Warner, R. C.; Charman, S. A.; Wang, X.; Vennerstrom, J. L.; and Davis, P. H., "Derivatives of a benzoquinone acyl hydrazone with activity against Toxoplasma gondii" (2018). Biology Faculty Publications. 98.
https://digitalcommons.unomaha.edu/biofacpub/98

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.