Molecular network annotations from 43 Strychnos extracts based on their in vitro antiplasmodial activities in order to detect and target new alkaloids potentially active against malaria

In previous studies, the plants of Strychnos genus showed interesting antiplasmodial activities during in vitro tests against Plasmodium falciparum species, and more precisely against the FCA 20 Ghana (chloroquine-sensitive) and W2 Indochina (chloroquine-resistant) strains. For example, the IC50 values of the roots ethyl acetate extract of Strychnos usambarensis were 0.457 ± 0.005 μg/mL for FCA 20 Ghana, and 0.039 ± 0.0029 μg/mL for W2 Indochina. These activities were associated with the presence of active alkaloids such as 3', 4'- dihydrousambarensine with IC50 values of 0.857 ± 0.061 μM for FCA 20 Ghana, and 0.032 ± 0.002 μM for W2 Indochina. The alkaloid content and the diversity of 43 methanolic crude extracts from 28 Strychnos species were explored within a molecular network, and various metabolites already described in the literature were identified. In order to detect and target unknown alkaloids potentially active against malaria, an additional annotation was applied in the molecular network by adding data of the in vitro antiplasmodial activities (n=3) from 43 Strychnos extracts studied. Several interesting metabolites were observed close to usambarensine and its derivatives, sungucine, strychnogucine, and strychnofoline. This study is a proof that the Strychnos genus, despite the numerous studies carried out in the past, are still a promising source of new bioactive substances. Bio-guided and mass-guided fractionation will allow the isolation of alkaloids of interest in order to characterize and identify them, and to determine their activities against malaria.