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Casearia coriacea Vent., an endemic plant from the Mascarene Islands, was investigated following its antiplasmodial potentialities highlighted during a previous screening. Three clerodane diterpene compounds were isolated and identified as being responsible for the antiplasmodial activity of the leaves of the plant: caseamembrin T (1), corybulosin I (2), and isocaseamembrin E (3), which exhibited half maximal inhibitory concentrations (IC50) of 0.25 to 0.51 µg/mL. These compounds were tested on two other parasites, Leishmania mexicana mexicana and Trypanosoma brucei brucei, to identify possible selectivity in one of them. Although these products possess both antileishmanial and antitrypanosomal properties, they displayed selectivity for the malaria parasite, with a selectivity index between 6 and 12 regarding antitrypanosomal activity and between 25 and 100 regarding antileishmanial activity. These compounds were tested on three cell lines, breast cancer cells MDA-MB-231, pulmonary adenocarcinoma cells A549, and pancreatic carcinoma cells PANC-1, to evaluate their selectivity towards Plasmodium. This has not enabled us to establish selectivity for Plasmodium, but has revealed the promising activity of compounds 1-3 (IC50 < 2 µg/mL), particularly against pancreatic carcinoma cells (IC50 < 1 µg/mL). The toxicity of the main compound, caseamembrin T (1), was then evaluated on zebrafish embryos to extend our cytotoxicity study to normal, non-cancerous cells. This highlighted the non-negligible toxicity of caseamembrin T (1).

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INTRODUCTION: Plants of the Strychnos genus, which include about 200 species, are used for multiple traditional purposes as hunting poison, for example, and have shown interesting pharmacological properties, especially curarizing and tetanizing, but also against malaria. Many monoterpene indole alkaloids have already been isolated and identified. Among them, there is strychnine, a famous alkaloid that can cause death by asphyxiation. OBJECTIVE: Investigate alkaloidic molecular diversity from Strychnos genus using molecular networking technique and study the Strychnos genus from a chemotaxonomic point of view. MATERIAL AND METHODS: Twenty-eight different species and different plant parts were ground into powder using a grinder. The methanolic extracts were carried out using a pressurized solvent extraction and the alkaloid extract was performed manually with a separating funnel. The extracts were analyzed by HPLC-ESI(+)-Q/TOF. The data were processed using MZmine 2 software and the molecular network was generated on the GNPS platform. The study of the generated molecular network allowed the detection of various alkaloids. Among these is the famous strychnine which has been detected in 7 new Strychnos species not yet described as strychnine producers. This identification was investigated using orthogonal approaches, namely TLC, NMR, HPLC-UV and UHPLC-ESI(+)-Q/TOF analyses. The LOD by HPLC-UV of strychnine was also determined. RESULTS: Further analyses allowed to confirm the presence of strychnine in S. densiflora trunk barks but also to show the presence of strychnine with high probability in the trunk barks of S. camptoneura, S. congolana, S. boonei, and S. tchibangensis, and in the leaves of S. usambarensis. About the trunk barks of S. tricalyisoides, the probability of a strychnine content remains low. CONCLUSION: This work exemplified the efficiency of molecular networking in identifying known metabolites (major and minor alkaloids) involved in the chemotaxonomic study of plants from Strychnos genus.

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