Bioactive Clerodane Diterpenoids from the Leaves of <i>Casearia coriacea</i> Vent
Allison Ledoux,
Carla Hamann,
Olivier Bonnet,
Kateline Jullien,
Joëlle Quetin-Leclercq,
Alembert Tchinda,
Jacqueline Smadja,
Anne Gauvin-Bialecki,
Erik Maquoi,
Michel Frédérich
Affiliations
Allison Ledoux
Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Avenue Hippocrate 15, 4000 Liège, Belgium
Carla Hamann
Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Avenue Hippocrate 15, 4000 Liège, Belgium
Olivier Bonnet
Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Avenue Hippocrate 15, 4000 Liège, Belgium
Kateline Jullien
Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Avenue Hippocrate 15, 4000 Liège, Belgium
Joëlle Quetin-Leclercq
Pharmacognosy Research Group, Louvain Drug Research Institute, LDRI, Université Catholique de Louvain, UCLouvain, Avenue E. Mounier, B1 72.03, B-1200 Brussels, Belgium
Alembert Tchinda
Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Avenue Hippocrate 15, 4000 Liège, Belgium
Jacqueline Smadja
Laboratoire de Chimie des Substances Naturelles et des Sciences des Aliments, Université de Réunion, Avenue René Cassin 15, BP 7151, 97715 Saint-Denis, La Réunion, France
Anne Gauvin-Bialecki
Laboratoire de Chimie des Substances Naturelles et des Sciences des Aliments, Université de Réunion, Avenue René Cassin 15, BP 7151, 97715 Saint-Denis, La Réunion, France
Erik Maquoi
Laboratory of Biology of Tumor and Development, GIGA/CIRM, University of Liège, Avenue Hippocrate 15, 4000 Liège, Belgium
Michel Frédérich
Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Avenue Hippocrate 15, 4000 Liège, Belgium
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 50 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).
