Several compounds, structurally related to the insect-growth regulator Fenvxycarb (l), were designed and synthesized. These compounds were tested as growth inhibitors of Trypanmvma cruzi cells (epimastigotes). Compounds 6,16, 18, and 22 were very active against 7'. cruzi making them promising good candidates either for blood-bank sterilization or Chugus'-disease surveillance, while compounds 11, 12,13, and 19 showed a moderate degree of activity.
Introduction. -The flagellate protozoan Trypanosoma cruzi is the causative agent of Chagas' disease which is transmitted to the human body by insects of the family Reduviidae, specially Triatoma injectans, and also by transfusion of infected blood. Despite of the progresses made in chemotherapy, new compounds are needed, because the trypanocidal drugs presently in use, Nifurtimox and Benznidazole, cause considerable side effects on patients and present lack of efficacy and specificity against all stages of the disease [l-31. There is no effective treatment available for Chagas' disease in spite of the important advances made in the study of the biochemistry of the microorganism responsible for the mentioned disease. The urgency for more selective and less toxic drugs led to evaluate chemical therapy based on the knowledge of T. cruzi biochemistry and the mode of action of these compounds. In addition, due to the risk that T. cruzi may be transmitted in blood banks for transfusions, it is very important to have new compounds to kill this parasite in blood to be transfused. At present, the drug in use for this purpose, Gentian Violet, suffers from serious limitations concerning its safety [3].
In previous works, several juvenile-hormone analogues which presented a reasonable degree of activity against Chagas' disease vector, Le., the insect Triatoma infestans [S], were tested against the microorganism T . cruzi (epimastigotes) taking into account that those insects, after treatment with juvenile-hormone analogues, were less susceptible to gut natural infections with T. cruzi than normal nontreated insects [6]. Surprisingly, they showed a variable degree of activities, some of them were very active compounds in inhibiting cell proliferation of this parasite [7] [8]. Our goal was that these compounds, formerly juvenile-hormone analogues, became cell-growth inhibitors. At the beginning, the well-known juvenile-hormone analogue Fenoxycarb (ethyl [2-(4-phenoxyphenoxy)ethyllcarbamate; 1) was employed as standard control, because it behaved as a highly active agent against eggs and nymphal stages of T. infestans. However, some modified 'H-NMR spectrum (cj: 1131). Anal. HPLC showed 6 to be pure (no (2)-isomer present).
') Better yields were obtained, when BH,. THF was freshly prepared and used immediately according to Brown's methodology, see (141.