Glucose-6-phosphate dehydrogenase is the target for the trypanocidal action of human steroids

Cytosolic NADPH Homeostasis in Glucose-starved Procyclic Trypanosoma brucei Relies on Malic Enzyme and the Pentose Phosphate Pathway Fed by Gluconeogenic Flux

“…We also conclude that the degree of RNAi-mediated repression of G6PDH is limiting for NADPH production but not for ribose synthesis. The genetic interaction was confirmed by chemical inhibition of T. brucei G6PDH by DHEA, a specific inhibitor of G6PDH in T. brucei (20,21,44). We determined the LD 50 of this compound for the procyclic ⌬mec line to be 18 M after 48 h of incubation (Fig.…”

Glucose-6-Phosphate Dehydrogenase of Trypanosomatids: Characterization, Target Validation, and Drug Discovery

“…Inhibitors were tested on the cell growth of a trypanosome clone that has been created to also express a transgene encoding this L. mexicana enzyme [59]. Whereas wild-type bloodstream form T. brucei showed a dose-dependent killing by DHEA and EA with ED 50 values of 41.8 ± 2.1  μ M and 21.4 ± 1.6  μ M, respectively, the T .…”

“…Whereas wild-type bloodstream form T. brucei showed a dose-dependent killing by DHEA and EA with ED 50 values of 41.8 ± 2.1  μ M and 21.4 ± 1.6  μ M, respectively, the T . brucei ( Lm G6PDH) transgenic parasites showed no growth inhibition whatsoever by the two compounds, even at concentrations up to 100  μ M [59]. Thus, transfection of T. brucei bloodstream form parasites with Lm G6PDH could rescue the trypanosomes from being killed by DHEA and EA.…”

Compounds from <em>Terminalia mantaly</em> L. (Combretaceae) Stem Bark Exhibit Potent Inhibition against some Pathogenic Yeasts and Enzymes of Metabolic Significance<strong></strong>

“…In contrast, G6PD-deficient tumor cell lines showed relatively slow growth and enhanced apoptosis [41]. Previous studies also reported G6PD inhibitory properties for few compounds such as steroids and derivatives [42,43], chalcones [28], catechin gallates [44], and some phenolic molecules [45].…”