Ontology highlight
ABSTRACT:
SUBMITTER: Meco-Navas A
PROVIDER: S-EPMC6142067 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Meco-Navas Alejandro A Ebiloma Godwin U GU Martín-Domínguez Ana A Martínez-Benayas Irene I Cueto-Díaz Eduardo J EJ Alhejely Amani Saud AS Balogun Emmanuel O EO Saito Machi M Matsui Miho M Arai Natsumi N Shiba Tomoo T Harada Shigeharu S de Koning Harry P HP Dardonville Christophe C
ACS medicinal chemistry letters 20180731 9
The SAR of 4-hydroxybenzaldehyde inhibitors of the trypanosome alternative oxidase (TAO), a critical enzyme for the respiration of bloodstream forms of trypanosomes, was investigated. Replacing the aldehyde group with a methyl ester resulted in a 10-fold increase in TAO inhibition and activity against <i>T. brucei</i>. Remarkably, two analogues containing the 2-hydroxy-6-methyl scaffold (<b>9e</b> and <b>16e</b>) displayed single digit nanomolar TAO inhibition, which constitute the most potent 4 ...[more]