Abstract :
[en] The plants of the Strychnos genus were the subject of much research both for their tetanizing and curarizing properties, and for their multiple traditional uses. Among these, we can mention the treatment against snake bites, bronchitis, rheumatism and fevers. In previous researches, promising antiplasmodial activities against chloroquine-sensitive and/or chloroquine-resistant strains of Plasmodium falciparum (CQS and CQR, respectively) were demonstrated. This is notably the case for the ethyl acetate extract of Strychnos usambarensis roots (IC50 of 0.457 ± 0.005 µg/mL (CQS) and 0.039 ± 0.0029 µg/mL (CQR)). Many alkaloids were isolated from these species such as 3',4'-dihydrousambarensine, isolated from the roots of S. usambarensis and active against chloroquine-susceptible and chloroquine-resistant strains of P. falciparum (IC50 of 0.857 ± 0.061 µM (CQS) and 0.032 ± 0.002 µM (CQR)).
With the development of dereplication tools, including molecular networking, we could explore the metabolites of 43 methanolic crude extracts obtained from different parts of 28 Strychnos species. Through the development of shared spectral databases such as MIADB, which contains a large panel of mass spectra of monoterpene indole alkaloids, we could discriminate known from unknown metabolites. Among the known molecules, we identified strychnine, icajine, sungucine, usambarensine, strychnofoline, and many others. To explore the molecular network in detail, it was classified using the MolNetEnhancer workflow. In addition, a biological dimension was added as metadata based on an evaluation of the antiplasmodial activities of the 43 methanolic crude extracts, determined from 3 independent experiments. The different levels of biological activities were divided into 5 levels to facilitate the exploitation of the molecular network. The exploration of the molecular network allowed to highlight new potentially active alkaloids. This is for example the case of alkaloids with masses m/z 408.2434, 447.2552, 463.2373 and 893.5042, not identifiable in the dictionary of natural products, and present in the cluster of usambarensine and its derivatives. These are probably derivatives of usambarensine, whose structure remains to be elucidated. Other interesting metabolites were also detected in the sungucine and strychnogucine B cluster as well as in the strychnofoline cluster.
This study demonstrates that plants of the Strychnos genus remain a promising source of new bioactive substances, and that, thanks to the advent of various dereplication tools, this offers us new leads for the identification of high added value molecules.
