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

• Published in: Experimental parasitology 2017-06, Vol.177, p.57-65
• Main Authors: da Silva, Aline Caroline, dos Santos, Thiago André Ramos, da Silva, Isis Viviane Bezerra, de Oliveira, Marcos Victor Gregório, Moreira, Diogo Rodrigo Magalhães, Leite, Ana Cristina Lima, Pereira, Valéria Rêgo Alves
• Format: Article
• Language: English
• Subjects: Animals; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Apoptosis; Chemotherapy; Cutaneous leishmaniasis; Immunologic Factors - chemistry; Immunologic Factors - pharmacology; Immunologic Factors - toxicity; Inhibitory Concentration 50; Interleukin-10 - metabolism; Interleukin-12 - metabolism; Leishmania mexicana - drug effects; Leishmania mexicana - immunology; Leishmaniasis, Cutaneous - drug therapy; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - parasitology; Male; Mice; Mice, Inbred BALB C; Necrosis; Nitric Oxide - metabolism; Structure-Activity Relationship; Synthetic compound; Thiosemicarbazone; Thiosemicarbazones - chemistry; Thiosemicarbazones - pharmacology; Thiosemicarbazones - toxicity; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2017.04.003

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/00LTB 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 extracellular 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. [Display omitted] •Aryl thiosemicarbazone derivatives have low toxicity to host cells.•Aryl thiosemicarbazone demonstrated direct activity on L. amazonensis in vitro.•Macrophage Modulation by cytokines TNF, IL-10, IL-12 and nitric oxide was detected.