Study of in vitro biological activity of thiazoles on Leishmania (Leishmania) infantum.

OBJECTIVES: In the prospection of possible agents against neglected diseases, thiazole compounds are presented as promising candidates and are known to have activity against trypanosomatid parasites. Thus, this work aimed to evaluate the effects of thiazole compounds on Leishmania infantum, the aetiological agent of visceral leishmaniasis. METHODS: Thiazole compounds (five thiazoacetylpyridines [TAPs-01, -04, -05, -06, -09) and five thiazopyridines [TPs-01, -04, -05, -06, -09]) were tested regarding their leishmanicidal activity on both promastigote and amastigote forms of L. infantum. Cytotoxicity was tested using peritoneal macrophages of BALB/c mice. Ultrastructural analyses were performed to identify possible intracellular targets of the most effective compound on promastigote forms. To observe routes that can clarify the possible mechanism of action of the compounds on the intracellular amastigote forms, the nitrite dosage was performed. RESULTS: All compounds inhibited the growth of promastigote and presented low cytotoxicity, being more selective to the parasite than to mammalian cells. All compounds tested were able to decrease macrophage infection. There was a significant decrease in the survival rate of the amastigote when compared with the untreated cells, with TAP-04 presenting the best index. TAP-04 induced ultrastructural changes that are related to cell death by apoptosis. None of the macrophage groups infected with L. infantum and subsequently treated showed increased nitrite release. CONCLUSIONS: The low toxicity to mammalian cells and the leishmanicidal activity observed demonstrate that the synthesis of drugs based in thiosemicarbazone nucleus, thiazole and pyridine derivatives are promising for the treatment of visceral leishmaniasis.

Effects of intratesticular injection of zinc-based solution in rats in combination with anti-inflammatory and analgesic drugs during chemical sterilization.

AIM: Chemical sterilization is a non-surgical method of contraception based on compounds injected into the testis to induce infertility. However, these injections can cause discomfort and pain able to impair the recovery of animals after this treatment. The objective of this study was to investigate if anti-inflammatories or pain relievers inhibited the sterilizing effect of zinc gluconate-based solution on the testis. MATERIALS AND METHODS: Adult rats were treated in groups: G1 (control), G2 (dimethyl sulfoxide + dipyrone); G3 (dipyrone/zinc); G4 (dipyrone + celecoxib/zinc); G5 (dipyrone + meloxicam/zinc), and G6 (dipyrone + dexamethasone/zinc) in a single dose per day during 7 days. Animals were analyzed at 7, 15, and 30 days after treatments. RESULTS: The zinc-induced a widespread testicular degeneration and decreased testosterone levels even in combination with anti-inflammatories or pain relievers. Testis, epididymis, prostate, and seminal vesicle had a weight reduction. The anti-inflammatory effect of dexamethasone interfered in the desired action of zinc gluconate in the 1st 15 days and celecoxib up to 7 days. CONCLUSION: Meloxicam plus dipyrone did not impair the chemical sterilization based on zinc gluconate, and it can be used to reduce nociceptive effects in animals after chemical sterilization.