Bioactive Clerodane Diterpenoids from the Leaves of Casearia coriacea Vent

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 3; p. 1197
• Main Authors: Ledoux, Allison, Hamann, Carla, Bonnet, Olivier, Jullien, Kateline, Quetin-Leclercq, Joëlle, Tchinda, Alembert, Smadja, Jacqueline, Gauvin-Bialecki, Anne, Maquoi, Erik, Frédérich, Michel
• Format: Journal Article Web Resource
• Language: English
• Published: Switzerland MDPI AG 25-01-2023; MDPI
• Subjects: Adenocarcinoma; Analytical chemistry; Animals; Antimalarials - pharmacology; Antiprotozoal agents; Bioassays; Biocompatibility; Breast cancer; caseamembrin T; Casearia; Casearia coriacea; Cellular Biology; Chemical Sciences; clerodane diterpenoids; corymbulosin I; Cytotoxicity; Disease prevention; Diterpenes; Diterpenes, Clerodane - pharmacology; Drug Discovery; Drugs; Embryos; Endemic plants; Fractionation; Human health sciences; isocaseamembrin E; Leaves; Life Sciences; Lung cancer; Malaria; Natural products; Organic Chemistry; Pancreatic carcinoma; Pancreatic Neoplasms; Parasites; Pharmaceutical Science; Pharmacie, pharmacologie & toxicologie; pharmacognosy; Pharmacy, pharmacology & toxicology; Plant Extracts - pharmacology; Plant Leaves; Plants; Plasmodium; Sciences de la santé humaine; Selectivity; Toxicology; Tumor cell lines; Vector-borne diseases; Zebrafish; Mascarene Islands; Plasmodium; Casearia coriacea; corymbulosin I; isocaseamembrin E; caseamembrin T; clerodane diterpenoids
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28031197

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 (
), corybulosin I (
), and isocaseamembrin E (
), which exhibited half maximal inhibitory concentrations (IC
) of 0.25 to 0.51 µg/mL. These compounds were tested on two other parasites,
and
, 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
. This has not enabled us to establish selectivity for
, but has revealed the promising activity of compounds
-
(IC
< 2 µg/mL), particularly against pancreatic carcinoma cells (IC
< 1 µg/mL). The toxicity of the main compound, caseamembrin T (
), 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 (
).