Bioactive Clerodane Diterpenoids from the Leaves of Casearia coriacea Vent.

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 (IC 50 ) 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 (IC 50 < 2 µg/mL), particularly against pancreatic carcinoma cells (IC 50 < 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 ).