Synthesis and biological evaluation of thiazole derivatives as LbSOD inhibitors

J Enzyme Inhib Med Chem. 2019 Dec;34(1):333-342. doi: 10.1080/14756366.2018.1550752.

Abstract

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.

Keywords: Leishmania; superoxide dismutase; thermal shift assay; thiazole derivatives.

MeSH terms

  • Brazil
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Leishmania braziliensis / enzymology*
  • Molecular Structure
  • Structure-Activity Relationship
  • Superoxide Dismutase / antagonists & inhibitors*
  • Superoxide Dismutase / metabolism
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Enzyme Inhibitors
  • Thiazoles
  • Superoxide Dismutase

Grants and funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico [grant number CNPq 479160/2013-9].