Synthesis and evaluation trypanosomicidal activity of new derivatives of megazol

Helena B. Leites, Flávia S. Damasceno, Ariel M. Silber, Ronaldo Z. Mendonça, Cristina Northfleet de Albuquerque


Objective: This work aims at the synthesis of megazol analogs with antitrypanosomicidal activity. Chagas’disease is caused by Trypanosoma cruzi and is a debilitating disease that has both acute and chronic forms. Many South Americans suffer from the chronic form of Chagas’disease, and there is no treatment currently available.

Methods: In the chemical part, classical techniques of heterocyclic synthesis as well as usual methods of identification were used. In the biological part the cell proliferation test was used in vitro and the IC 50.

Results: We synthesized a series of derivatives of 2-(1-methyl-5-nitro-2-imidazolyl)-5-substituted-1,3,4-thiadiazoles where 1-acetyl, 1-propyl and 1-nonyl were used as the substituent (4,6,7). Derivatives without nitro group were also synthesized (3,12) along with thiosemicarbazones (8,9,10) and a 5-(5-nitro-2-furanyl)-1,3,4-thiadiazol-2-amine (11). These compounds were evaluated using an in vitro test where were measured the cell proliferation. The derivatives that obtained the best results underwent further tests, in which their IC50 was calculated. The data revealed that two compounds (4,6) were effective against the parasite (IC50= 0.354 µM; IC50= 2.13 µM) and besides that, obtained the same results as the positive control, antimycim and rotenone. All proposed structures were obtained in satisfactory yields and purities.

Conclusions: In conclusion, the in vitro trypanocidal activity makes these compounds promising leads in the development of an effective therapeutic agent. However, this study must be completed by additional tests with in vitro amastigote/macrophage models or in vivo mouse models. Analyzing the amide derivatives, compounds (4) and (6) were the ones that presented the best results.


5-nitroimidazole, 1,3,4-Thiadiazole, Megazol, Trypanosoma cruzi, Antichagasic activity

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