Structure-Activity Relationship of New Growth Inhibitors of Trypanosoma cruzi.

SZAJNMAN, S. H.; CINQUE, G. M.; ZHONG, L.; DOCAMPO, R.; RODRÍGUEZ, J. B.; GROS, E. G.

Caxambú, MG, Brazil

Congreso; XXV Annual Meeting on Basic Reasearch in Chagas’ Disease; 1998

Mem. Inst. Oswaldo Cruz,1998, 93 Suppl. II, 135.

As a part of our ongoing program aimed at the search for new chemotherapeutic agents to control Trypanosoma cruzi proliferation, we designed, synthesized and biologically evaluated a new series of compounds taken 4-phenoxyphenoxyethyl thiocyanate as lead drug. This compound had previously proved to be an extremely potent growth inhibitor of T. cruzi growth against epimastigotes and against the intracellular forms of the parasite. It is interesting to pointing out that this compound was much more active than two well known antiparasitic agents: nifurtimox and ketoconazole. In an attempt to improve the inhibitory action observed several structural modification were made, mainly at the aromatic moiety, keeping the thiocyanate group at the polar extreme, wich is responsible fot the ultrapotent activity observed. There is tantalizing evidence to believe that these drugs block the ergosterol biosynthetic pathway. A structure-activity study is presented.