IN-VITRO TRYPANOCIDAL ACTIVITY OF TETRAETHYLTHIURAM DISULFIDE AND SODIUM DIETHYLAMINE-N-CARBODITHIOATE ON TRYPANOSOMA-CRUZI

Tetraethylthiuram disulfide (disulfiram) (TETD) and sodium diethylamin e-N-carbodithioate (DECD) were examined for their in vitro trypanocida l activity against Trypanosoma cruzi. Benznidazole (BNZ), the drug use d clinically for the chemotherapy of Chagas' disease, was used as a po sitive control. Inhibition assays included evaluation against the epim astigote, trypomastigote, and amastigote forms. Tetraethylthiuram disu lfide and its reductive metabolite DECD inhibited 64.6% and 69.7%, res pectively, of epimastigotes at a concentration of 50 mu g/ml after 72 hr and BNZ caused 69.1% inhibition at the same concentration. Both TET D and DECD were not as effective against tissue culture trypomastigote s as BNZ (TETD = 47.7%,; DECD = 46.1%; BNZ = 88.7%) at 50 mu g/ml afte r 24 hr. However, TETD and DECD treatment of amastigote-infected 3T3 f ibroblasts yielded 60 and 67% inhibition, respectively, as compared to BNZ with an inhibition of 62%. A possible mechanism of action of TETD and DECD is via interference with the essential metal metabolism of T . cruzi. Since toxicity data for both TETD and DECD are available and both drugs are active against the parasite, these drugs are candidates for further study to determine if they are of potential clinical inte rest as a prophylactic or therapeutic agent against Chagas' disease.