A novel icetexane diterpene, 5-epi-icetexone from Salvia gilliessi is active against Trypanosoma cruzi.
In this work the effect of a novel compound, 5-epi-icetexone (ICTX) obtained from Salvia gilliessi Benth. (Labiatae), is studied on cultured epimastigotes of Trypanosoma cruzi (Tulahuen). It was found that the compound exerts an antiproliferative effect on the parasites at concentrations between 2.8 and 4.2 microM, and similar sensitivity in other strains (Dm28c, CL-Brener and Y-strain). The compound was deleterious at concentrations higher than 4.2 microM, with an estimated IC50 of 6.5+/-0.75 microM, but with low cytotoxicity to mammalian cells. These effects were irreversible, even at short times of exposure to the drug. In solution, ICTX showed to be stable for at least 96 h at 29 degrees C. With cytostatic dose a little percentage of parasites was resistant to the action of ICTX, and they continued growing although with different kinetic. By electron transmission microscopy, at dose of 4.2 microM an external vesiculization was observed on the first day of exposure to the compound, but the parasite cytoplasm became plenty of vacuoles and exhibited nuclear disorganization from the second day of exposure. It was concluded that ICTX is active against T. cruzi and may act by multiple mechanisms. In future, this novel icetexane diterpene may be a good candidate for therapeutic use against Chagas' disease.
Sanchez
A M
AM
Instituto de Histología y Embriología, Facultad de Ciencias Medicas, Universidad Nacional de Cuyo, CCcorreo 56, 5500 Mendoza, Argentina.
Jimenez-Ortiz
V
V
Sartor
T
T
Tonn
C E
CE
García
E E
EE
Nieto
M
M
Burgos
M H
MH
Sosa
M A
MA
D000818:Animals; D014355:Chagas Disease / Q000469:parasitology; D004224:Diterpenes / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D046529:Microscopy, Electron, Transmission; D010936:Plant Extracts / Q000494:pharmacology; D027544:Salvia / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure
D004224:Diterpenes; D010936:Plant Extracts; D014344:Trypanocidal Agents; C512853:icetexone