Aryl thiosemicarbazones: In vitro and immunomodulatory activities against L-amazonensis

作者：da Silva Aline Caroline^*; Ramos dos Santos Thiago Andre; Bezerra da Silva Isis Viviane; Gregorio de Oliveira Marcos Victor; Magalhaes Moreira Diogo Rodrigo; Lima Leite Ana Cristina; Alves Pereira Valeria Rego

来源：Experimental Parasitology, 2017, 177: 57-65.

DOI：10.1016/j.exppara.2017.04.003

• Cutaneous leishmaniasis
• Chemotherapy
• Synthetic compound
• Thiosemicarbazone

Leishmaniasis is an infection caused by different species of Leishmania genus. Currently, there is no vaccine available for Leishmania infections in humans and conventional treatments are limited due to side effects. Therefore, the development of,new antileishmanial drugs is an urgent need. In present study, we evaluated the cytotoxicity in host cells, leishmanicidal activity and immunomodulatory potential of seven aryl thiosemicarbazones. Host cell cytotoxicity was determined in peritoneal macrophages of BALB/c mouse, antiparasitic activity was determined against promastigotes and amastigotes of WHOM/OOLTB 0016 strain of L. amazonensis. Nitric oxide (NO) production, interleukin (IL)-12, IL-10 and TNF-alpha secretion were measured in the supernatant of uninfected and infected macrophage cultures. It was observed that aryl thiosemicarbazones presented in vitro antiparasitic activity against both extra cellular and intracellular forms of L amazonensis. However, unlike Amphotericin B, these compounds displayed low cytotoxicity towards host cells. In addition to observed antiparasitic activity, compounds exhibited modulatory properties in the secretion of cytokines and nitrite content from uninfected stimulated and L. amazonensis-infected macrophages. In conclusion, we demonstrated the in vitro antiparasitic activity against L amazonensis for aryl thiosemicarbazones, which is possible achieved by Th1 cytokine profile modulation. These findings are potential useful for drug development against cutaneous leishmaniasis.

• 出版日期2017-6