In Vitro Effects of Aminopyridyl Ligands Complexed to Copper(II) on the Physiology and Interaction Process of Trypanosoma cruzi

Tropical Medicine and Infectious Disease

article

Rafaela Silva-Oliveira¹  Leandro S. Sangenito¹  Andrew Reddy³  Trinidad Velasco-Torrijos⁴  André L. S. Santos¹  Marta H. Branquinha¹ 

[1] Laboratório de Estudos Avancados de Microrganismos Emergentes e Resistentes ,(LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro;Instituto Federal de Educação;Ferrier Research Institute, Victoria University of Wellington;Department of Chemistry, Maynooth University;The Kathleen Lonsdale Institute for Human Health Research, Maynooth University;Programa de Pós-Graduação em Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro

关键词: Trypanosoma cruzi;    Chagas disease;    metal complexes;    chemotherapy;   

DOI  :  10.3390/tropicalmed8050288

学科分类：社会科学、人文和艺术（综合）

来源: mdpi

【 摘 要 】

Chagas disease is derived from the infection by the protozoan Trypanosoma cruzi. In many countries, benznidazole is the only drug approved for clinical use despite several side effects and the emergence of resistant parasite strains. In this context, our group has previously pointed out that two novel aminopyridine derivatives complexed with Cu2+, namely, cis-aquadichloro(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamino)copper (3a) and its glycosylated ligand cis-dichloro (N-{[4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)pheny]lmethyl}-2-pyridinemethamino)copper (3b), are effective against T. cruzi trypomastigote forms. With this result in mind, the present work aimed to investigate the effects of both compounds on trypomastigotes physiology and on the interaction process with host cells. Apart from loss of plasma membrane integrity, an increased generation of reactive oxygen species (ROS) and decreased mitochondrial metabolism were observed. Pretreatment of trypomastigotes with these metallodrugs inhibited the association index with LLC-MK2 cells in a typical dose-dependent manner. Both compounds showed low toxicity on mammalian cells (CC50 100 µM), and the IC50 values calculated for intracellular amastigotes were determined as 14.4 µM for 3a and 27.1 µM for 3b. This set of results demonstrates the potential of these aminopyridines complexed with Cu2+ as promising candidates for further antitrypanosomal drug development.

【 授权许可】

CC BY