High antitrypanosomal activity of plant-derived sulphur-containing amides

International audienceChagas disease, caused by , represents an important public health problem in endemic geographic regions in Middle and South America, affecting 15 million infected people. Treatment options are still limited due to the toxicity of available drugs, parasite resistance and poor drug activity during the chronic phase of the disease. In this study, we investigated the in vitro antitrypanosomal activity of 15 tropical plant-derived compounds with the aim of finding new drug candidates. Three novel sulphur-containing amides (methyldambullin, methylgerambullin and sakambullin) showed promising high antitrypanosomal activities, with 50% effective concentrations (EC values) after 72h exposure of 1.7, 1.23 and 5.18μM, respectively, compared with EC values for amphotericin B and benznidazole of 0.71μM and 30.89μM, respectively

Mouse and human indoleamine 2,3-dioxygenase display some distinct biochemical and structural properties

The hemoprotein indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme in the most significant pathway for mammalian tryptophan metabolism. It has received considerable attention in recent years, particularly due to its dual role in immunity and the pathogenesis of many diseases. Reported here are differences and similarities between biochemical behaviour and structural features of recombinant human IDO and recombinant mouse IDO. Significant differences were observed in the conversion of substrates and pH stability. Differences in inhibitor potency and thermal stability were also noted. Secondary structural features were broadly similar but variation between species was apparent, particularly in the α-helix portion of the enzymes. With mouse models substituting for human diseases, the differences between mouse and human IDO must be recognised before applying experimental findings from one system to the next.8 page(s