Aryl thiosemicarbazones: In vitro and immunomodulatory activities against L. amazonensis Aline Caroline da Silva a, * , Thiago Andr  e Ramos dos Santos a , Isis Viviane Bezerra da Silva a , Marcos Victor Greg  orio de Oliveira c , Diogo Rodrigo Magalh ~ aes Moreira b , Ana Cristina Lima Leite c , Val  eria R ^ ego Alves Pereira a a Departamento de Imunologia, Centro de Pesquisas Aggeu Magalh~ aes, Recife, Pernambuco, Brazil b Laborat orio de Engenharia Tecidual e Imunofarmacologia, Centro de Pesquisas Gonçalo Moniz, Salvador, Bahia, Brazil c Departamento de Ci^ encias Farmac^ euticas, Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil highlights graphical abstract  Aryl thiosemicarbazone derivatives have low toxicity to host cells.  Aryl thiosemicarbazone demon- strated direct activity on L. amazonensis in vitro.  Macrophage Modulation by cytokines TNF, IL-10, IL-12 and nitric oxide was detected. article info Article history: Received 19 October 2016 Received in revised form 27 February 2017 Accepted 18 April 2017 Available online 19 April 2017 Keywords: Cutaneous leishmaniasis Chemotherapy Synthetic compound Thiosemicarbazone abstract 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 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. © 2017 Elsevier Inc. All rights reserved. 1. Introduction Leishmaniasis is a chronic disease caused by kinetoplastid pro- tozoa belonging to Leishmania genus, which are transmitted from * Corresponding author. E-mail address: aline.caroline.bm@gmail.com (A.C. da Silva). Contents lists available at ScienceDirect Experimental Parasitology journal homepage: www.elsevier.com/locate/yexpr http://dx.doi.org/10.1016/j.exppara.2017.04.003 0014-4894/© 2017 Elsevier Inc. All rights reserved. Experimental Parasitology 177 (2017) 57e65