Discovering original antiplasmodial compounds through mass-guided exploration of the alkaloid diversity in the Strychnos genus

Several monoterpene indole alkaloids from various plants of the Strychnos genus have shown promising antiplasmodial activity. In front of the parasites' growing resistance to existing treatments, the alkaloid content from 44 crude extracts of 28 Strychnos species are explored using the molecular networking technique with the aim of identifying new antimalarial compounds. Thanks to public MS/MS spectral databases and the antiplasmodial activities of studied crude extracts, clusters containing mainly unknown metabolites potentially active against malaria were highlighted and targeted. Exploring the annotated molecular network led to reveal unexpected presence of strychnine in seven species, and to select Strychnos usambarensis leaves and Strychnos longicaudata trunk barks for in-depth studies. Using bio- and mass-guided fractionation, several unknown metabolites were isolated, and are currently being identified using NMR and MS/MS data.