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 (IC50) of 0.25 to 0.51 mu g/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 mu g/mL), particularly against pancreatic carcinoma cells (IC50 < 1 mu g/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).

Automated summary

Casearia coriacea Vent., a plant endemic to the Mascarene Islands, exhibited potent antiplasmodial activity through the presence of three identified compounds, caseamembrin T (1), corybulosin I (2), and isocaseamembrin E (3), with IC50 values ranging from 0.25 to 0.51 μg/mL. While these compounds also showed antileishmanial and antitrypanosomal properties, they exhibited selectivity towards the malaria parasite with selectivity indices ranging from 6 to 12 and 25 to 100, respectively. Additionally, compounds 1-3 demonstrated promising activity against pancreatic carcinoma cells (IC50 < 1 μg/mL). However, the main compound, caseamembrin T (1), displayed significant toxicity when evaluated on zebrafish embryos.