Sesquiterpene lactones and the diterpene 5-epi-icetexone affect the intracellular and extracellular stages of Trypanosoma cruzi.
Chagas disease is a major health problem in Latin America and is caused by the parasitic protozoan Trypanosoma cruzi. Although many drugs have been used to alleviate the disease, these have been ineffective in the chronic phase and have also presented numerous side effects on patients. In this study we tested the effect of three sesquiterpene lactones (dehydroleucodine, helenalin and mexicanin) and a diterpene (5-epi-icetexone) on parasites (Y-strain) grown in host cells. At 48 h of treatment, the number of amastigotes inside the cells was lower than in the controls. This effect was observable at concentrations of 1.5-3.8 μM, which are of low cytotoxicity to host cells. In addition, the compounds caused a decrease in the percentage of infected cells. The treatments also reduced the presence of trypomastigotes in the extracellular medium. In all cases, helenalin was the most potent. The number of parasites per cell at 24h indicates the occurrence of multiple infection, which would also be affected by the compounds. However, we should not discard an effect on the proliferation and survival of parasites within the host cells. On the other hand, an additional effect on the differentiation of parasites and/or the survival of extracellular trypomastigotes might be possible. We conclude that these compounds are very effective against T. cruzi possibly by multiple mechanisms.
Laboratorio de Biología y Fisiología Celular, Dr. Francisco Bertini, Instituto de Histología y Embriología, Facultad de Ciencias Médicas, Universidad de Cuyo, Mendoza, Argentina.
Esteban
E
Lozano
Patricia
P
Barrera
Romina
R
Salinas
Israel
I
Vega
Matías
M
Nieto
Carlos
C
Tonn
Ulrike
U
Kemmerling
Renato A
RA
Mortara
Miguel A
MA
Sosa
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
D000981:Antiprotozoal Agents; D004224:Diterpenes; D007783:Lactones; D012717:Sesquiterpenes; C512853:icetexone