Synthesis, in vitro schistosomicidal activity and ultrastructural alterations caused by thiosemicarbazones and thiazolidinones against juvenile and adult Schistosoma mansoni worms (Sambon, 1907).

Schistosomiasis is a neglected disease that affects about 258 million people worldwide. Caused by Schistosoma mansoni, helminth which, in Brazil, it is present on 19 states and capital. Praziquantel (PZQ) treatment presents low efficacy and adverse effects in parasites juvenile stages. Thiosemicarbazones and thiazolidinones are rising as potent chemical groups that have biological activity wide spectrum, and with radical modifications, they may become more effective and selective. Aiming to evaluate the action of these molecules against S. mansoni, JF series thiosemicarbazones and thiazolidinones (LqIT/UFPE) were synthesized: JF30, JF31, JF33, JF34, JF35, JF36, JF38, JF39, JF42 and JF43. Several parameters were evaluated, such as: their cytotoxicity in VERO cells, in vitro schistosomicidal activity for juvenile and adult worms and their action on worms through ultrastructural changes. Cytotoxicity indices ranged from 272 µM to 725 µM. When evaluating mortality rate, adult and juvenile worms showed 100 % mortality rate within 24 h and 48 h, respectively, when exposed to the compounds JF31 and JF43 at a dose of 200 µM. Also, motility, mortality and oviposition parameters were evaluated: JF31 and JF43 presented a score of 0 in 24 h, meaning total absence of movement, whereas no eggs and soft tissue damage were observed under optical microscopy. Through scanning electron microscopy, integumentary alterations caused by the compounds JF31 and JF43 were observed, such as: exposure of the musculature, formation of integumentary bubbles, integuments with abnormal morphology and destruction of tubercles and spikes. The results shoerd that the compound JF31 was 2.39 times more selective for adult worms and JF43 was 3.74 times more selective for juvenile worms. Thus, the compounds JF43 and JF31 are the most promising for presenting schistosomicidal activity of S. mansoni.

Evaluation of anti-inflammatory effect of derivative (E)-N-(4-bromophenyl)-2-(thiophen-2-ylmethylene)-thiosemicarbazone.

The present study aimed to further investigate the anti-inflammatory activity of (E)-N-(4-bromophenyl)-2-(thiophen-2-ylmethylene)-thiosemicarbazone (BTTSC) as well as its antinociceptive effects. The anti-inflammatory activity was assessed using the model of ear edema induced by croton oil-induced and also evaluated in models of paw edema carrageenan-induced and by compound 48/80. Evaluation of the antinociceptive effect was performed through formalin test. In the nociception test induced by formalin the BTTSC showed activity in both phases of the pain, highlighting inflammatory pain, where it was able to reduce the time to paw lick 62.3, 84.30 and 100% at doses of 30, 100 and 300mgkg(-1). The anti-inflammatory activity was performed ear edema induced by croton oil, where none of the doses tested was capable of significantly regress edema. The paw edema carrageenan-induced showed activity compound, where the edema was reduced by 81.9 and 83.2% in the first two times of the experiment at the highest dose used. The paw edema assay induced by compound 48/80, showed that BTTSC after 15min of the inoculum phlogistic agent showed significant reduction of edema with values of 56.53% at a dose of 30mgkg(-1). Our results suggesting this compound exerts its antinociception effects connected with peripheral mechanisms. Furthermore, the compound was able to act in two phases of inflammation carrageenan-induced, highlighting the initial phase. This suggests an action on the early mediators of inflammation. The paw edema assay induced by compound 48/80 confirmed our hypothesis indicating action of the compound via histamine.