The antiproliferative effect of icetexane on cultured Trypanosoma cruzi.

A.M. SANCHEZ; T. SARTOR; C. TONN; M. NIETO; M.A. SOSA; M.H. BURGOS

Mendoza, Argentina

Congreso; XXI Annual Scientific Meeting. Cuyo Biology Society; 2003

Sociedad Biologia de Cuyo

Trypanosoma cruzi is the etiological agent of Chagas´ disease. Since decades, several trypanocidal substances have been used against the parasite, many of which have been isolated from plants. Here, we studied the effect of Icetexane 1 (ICTX), an hydroxylated quinone isolated from specimens of Salvia gilliesi, on the growth of cultured epimastigotes of T. cruzi. We observed that ICTX inhibited the proliferation of the parasites at concentrations between I and 3.5 µg/ml with very low mortality. At higher concentrations the compound turned to be deleterious, with an estimated IC50 of 6 µg/mL. The antiproliferative effect of ICTX was irreversible, even at short times of exposure. In order to know whether the quinone blocked a punctual step of the cell cycle we sudied the effect of the compound at different time points in synchronized parasites. They were exposed to hydroxyurea (HU) for 24 h, and after remotion of HU, parasites re-initiated their cell cycle from the phase S. We observed that the most important antiproliferative effect of ICTX ocurred when this drug is added during phase S (7-8 h), although we also observed an effect when the compound is added between 12-15 h after remotion of HU. Whether ICTX affects the activity of certain enzymes involved in DNA synthesis remains to be determined