In vitro Evaluation the Effect of 1, 3, 4, Thiadiazole New Derivatives against Leishmania Major

The main therapeutic compounds available against Leishmaniasis disease is pentavalent antimonyfcg compounds i.e. Glucantime and Pentostam. New antileishmanial compound is needed due to the emerge of drug-resistant leishmania agents in recent years. In the present study the antileishmanial activity of new 1, 3, 4 thiadiazole derivatives were evaluated. Promastigote stages of the parasites were cultured in RPMI-1640 containing 10% FBS, 100 IU/ml penicillin and 100 µg/ml streptomycin. Mouse peritoneal exudate macrophages (MPEM) isolated from the peritoneal cavity of BALB/c mice were used and the macrophages were counted and the cell suspension was adjusted to 5×105 cell/ml. Macrophage monolayers in 8-well chamber slides were infected with stationary phase promastigote, at a 5:1 parasite/cell proportion and incubated at 37oC and 5% CO2. Serial dilution of thiadiazole compounds and tartar emetic as the control was added to the slide chambers and parasite survival index (PSI) was measured after 5 days. The Thiazolyl blue reduction (MTT test) was used to determine the antileishmanial effect of the compounds on extra cellular forms of the parasite and after 72 h. The OD's were read by 96-well scanner and IC50 were calculated. Two thiadiazole compounds showed 6-67% antileishmanial activity in 4.6µg/ml concentration against intracellular forms of the parasites and also in MTT assay IC50 of 3.6 -7.6 µg/ml was determined. Due to high antileishmanial activity of some compounds, further studies on structure and activity of these compounds and new highly active derivatives is expected.