The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target

Tools

Wilkinson, Craig and McPhillie, Martin J and Zhou, Ying and Woods, Stuart and Afanador, Gustavo A and Rawson, Shaun and Khaliq, Farzana and Prigge, Sean T and Roberts, Craig W and Rice, David W and McLeod, Rima and Fishwick, Colin W and Muench, Stephen P (2014) The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target. Bioorganic and Medicinal Chemistry Letters, 24 (3). pp. 911-916. ISSN 0960-894X (https://doi.org/10.1016/j.bmcl.2013.12.066)

Full text not available in this repository.Request a copy

Abstract

The enoyl acyl-carrier protein reductase (ENR) enzyme of the apicomplexan parasite family has been intensely studied for antiparasitic drug design for over a decade, with the most potent inhibitors targeting the NAD(+) bound form of the enzyme. However, the higher affinity for the NADH co-factor over NAD(+) and its availability in the natural environment makes the NADH complex form of ENR an attractive target. Herein, we have examined a benzimidazole family of inhibitors which target the NADH form of Francisella ENR, but despite good efficacy against Toxoplasma gondii, the IC50 for T. gondii ENR is poor, with no inhibitory activity at 1μM. Moreover similar benzimidazole scaffolds are potent against fungi which lack the ENR enzyme and as such we believe that there may be significant off target effects for this family of inhibitors.

ORCID iDs

Wilkinson, Craig, McPhillie, Martin J, Zhou, Ying, Woods, Stuart ORCID logoORCID: https://orcid.org/0000-0002-3798-2074, Afanador, Gustavo A, Rawson, Shaun, Khaliq, Farzana, Prigge, Sean T, Roberts, Craig W ORCID logoORCID: https://orcid.org/0000-0002-0653-835X, Rice, David W, McLeod, Rima, Fishwick, Colin W and Muench, Stephen P;
CORE (COnnecting REpositories)