Quest for New Lead Compounds Against Malaria Based on Natural Prodrugs Present in Nauclea pobeguinii and Their Metabolites

The phytochemical composition of N. pobeguinii, used for treatment of malaria, was comprehensively characterized using UHPLC-UV-HRMS data. A diversity of compounds was detected, mainly alkaloids and saponins. Previous studies on strictosamide, the putative active constituent, showed no in vitro activity while the extract showed moderate in vitro activity [1]. It is suggested that metabolites of phytochemicals present in N. pobeguinii, most likely alkaloids, are responsible for its medicinal effect. An in vitro gastrointestinal model was used to simulate in vivo biotransformation of an extract of the plant and strictosamide itself. Analysis of these samples allowed the monitoring of the relative abundances of individual compounds over time. XCMS and EDGE were used to extract significant differential profiles from the raw longitudinal multiclass LC-MS data. An interactive Shiny app in R was used to rate the quality of the resulting features.

These ratings were used to train a random forest model. In general, glycosylated alkaloids showed a decrease in intensity over time. Alkaloids containing no sugar moieties, including angustine-type alkaloids, showed no gastrointestinal biotransformation. Prominent differences were observed between biotransformation of strictosamide present as a pure compound and the compound present in the extract. The characterized biotransformed extract was purified and tested for in vitro activity against malaria. Multivariate data analysis using OPLS-DA proposed alkaloids with a β-carboline moiety as active principles, suggesting that antiplasmodial activity of N. pobeguinii derives from an additive or synergistic effect of multiple minor alkaloids present in the bark extract and their metabolites.

• Reference

• 1 Mesia K, Cimanga RK, Dhooghe L. et al. . J Ethnopharmacol 2010; 131: 10-16

Publication History

Article published online:
12 December 2022