In vitro and in vivo activities of multi-target phtalimido-thiazoles on Schistosomiasis mansoni.

Schistosomicidal activity of six phthalimido-thiazoles derivatives with substitutions at the position three of the thiazole ring were analyzed in an experimental model. The substituents biphenyl (2i) and 2- naphthyl (2j) at a concentration of 80 µg/mL caused 100% mortality of the parasite in culture after 24 h and 48 h respectively. An evaluation of ultrastructural parasites showed damage in the tegument, formation of bubbles and partial destruction of the tubercles. The in vivo anti-parasitic activity with the derivate 2i was performed by administering it orally and intraperitoneally in a 400 mg/kg/5days regimen. Decreases in the number of eggs in the gut (45.1%) and a reduction of the percentage of mature (23.7%) and increased unviable (53.8%) eggs were observed. Our results also showed a reduction in the number of recovered worms after treatment with 2i (oral administration: 81, 25%). The results demonstrated that the prototypes which were tested had a significant anti-schistosomal effect against S. mansoni, suggesting that these derivatives are promising candidates for further research into the chemotherapy of schistosomiasis.

Synthesis, anticancer activity and mechanism of action of new thiazole derivatives.

Thiazole derivatives are recognized to possess various biological activities as antiparasitic, antifungal, antimicrobial and antiproliferative. The present work reports the synthesis of 22 new substances belonging to two classes of compounds: thiosemicarbazones and thiazoles, with the purpose of developing new drugs that present high specificity for tumor cells and low toxicity to the organism. A cytotoxic screening was performed to evaluate the performance of the new derivatives in five tumor cell lines. Eight compounds were shown to be promising in at least three tumor cell lines. These compounds had their IC50 determined within 72 h and the activity structure ratio was assessed. The effect of the best compounds on PBMC and hemolytic activity assay was then evaluated. The compound 1d was considered the most promising among the samples tested and its influence on cell cycle, DNA fragmentation and mitochondrial depolarization was evaluated.

Phthalimido-thiazoles as building blocks and their effects on the growth and morphology of Trypanosoma cruzi.

Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 6-7 million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases; however, its efficacy during the symptomatic chronic phase is controversial. The present work reports the synthesis and anti-T. cruzi activities of a novel series of phthalimido-thiazoles. Some of these compounds showed potent inhibition of the trypomastigote form of the parasite at low cytotoxicity concentrations in spleen cells, and the resulting structure-activity relationships are discussed. We also showed that phthalimido-thiazoles induced ultrastructural alterations on morphology, flagellum shortening, chromatin condensation, mitochondria swelling, reservosomes alterations and endoplasmic reticulum dilation. Together, these data revealed, for the first time, a novel series of phthalimido-thiazoles-structure-based compounds with potential effects against T. cruzi and lead-like characteristics against Chagas disease.