Synthesis and biological evaluation of thiazole derivatives as LbSOD inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry

Hélder Vinicius Carneiro da Silva¹  Julianna F. C. de Albuquerque¹  Rafael Matos Ximenes¹  Ivanildo Mangueira da Silva²  Antonio Rodolfo de Faria³  Daci José Brondani³  Camila C. Bitencourt Brito⁴  Marcelo Santos Castilho⁵ 

[1] Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife, PE, Brazil;Departamento de Farmácia, Universidade Federal de Pernambuco, Recife, PE, Brazil;Faculdade de Belo Jardim, Recife, PE, Brazil;Programa de pós-graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil;Programa de pós-graduação em Biotecnologia, Universidade Estadual de Feira de Santana, Feira de Santana, BA, Brazil;Faculdade de Farmácia, Universidade Federal da Bahia, Salvador, BA, Brazi;

关键词: Leishmania;    superoxide dismutase;    thiazole derivatives;    thermal shift assay;   

DOI  :  10.1080/14756366.2018.1550752

来源: publisher

【 摘 要 】

Leishmaniasis is considered as one of the major neglected tropical diseases due to its magnitude and wide geographic distribution. Leishmania braziliensis, responsible for cutaneous leishmaniasis, is the most prevalent species in Brazil. Superoxide dismutase (SOD) belongs to the antioxidant pathway of the parasites and human host. Despite the differences between SOD of Leishmania braziliensis and human make this enzyme a promising target for drug development efforts. No medicinal chemistry effort has been made to identify LbSOD inhibitors. Herein, we show that thermal shift assays (TSA) and fluorescent protein-labeled assays (FPLA) can be employed as primary and secondary screens to achieve this goal. Moreover, we show that thiazole derivatives bind to LbSOD with micromolar affinity.

【 授权许可】

CC BY