In vitro activity of N-phenyl-1,10-phenanthroline-2-amines against tachyzoites and bradyzoites of Toxoplasma gondii.

Autor: Martins-Duarte ES; Laboratório de Quimioterapia de Protozoários Egler Chiari, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 - Belo Horizonte, MG, Brazil; Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO) - Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Biomagem (INBEB), Rio de Janeiro, Brazil. Electronic address: ericamduarte@icb.ufmg.br., Portes JA; Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO) - Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Biomagem (INBEB), Rio de Janeiro, Brazil; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil., da Silva RB; Instituto de Química, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, Cidade Universitária, Rio de Janeiro, RJ, Brazil., Pires HS; Laboratório de Quimioterapia de Protozoários Egler Chiari, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 - Belo Horizonte, MG, Brazil., Garden SJ; Instituto de Química, Universidade Federal do Rio de Janeiro, Centro de Tecnologia, Bloco A, Cidade Universitária, Rio de Janeiro, RJ, Brazil., de Souza W; Centro Nacional de Biologia Estrutural e Bioimagem (CENABIO) - Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Biomagem (INBEB), Rio de Janeiro, Brazil; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2021 Nov 15; Vol. 50, pp. 116467. Date of Electronic Publication: 2021 Oct 11.
DOI: 10.1016/j.bmc.2021.116467
Abstrakt: Toxoplasma gondiiis an apicomplexan parasite, the causative agent of toxoplasmosis, a common disease in the world. Toxoplasmosis could be severe, especially in immunocompromised patients. The current therapy is limited, where pyrimethamine and sulfadiazine are the best choices despite being associated with side effects and ineffective against the bradyzoites, the parasitic form present during the chronic phase of the infection. Thus, new therapies against both tachyzoites and bradyzoites from T. gondii are urgent. Herein, we present the anti-T. gondii effect of 1,10-phenanthroline and its N-phenyl-1,10-phenanthroline-2-amine derivatives. The chemical modification of 1,10-phenanthroline tonew derivatives improved the anti-T. gondiiactivity 3.4 fold. The most active derivative presented ED 50 in the nanomolar range, the smallest value found was for Ph8, 0.1 µM for 96 h of treatment. The host cell viability was maintained after the treatment with the compounds, which were found to be highly selective presenting large selectivity indexes. Treatment with derivatives for 96 h was able to eliminate the T. gondii infection irreversibly. The ultrastructural alterations caused after the treatment with the most effective derivative (Ph8) included signs of cell death, specifically revealed by the Tunel assay for detection of DNA fragmentation. The Phen derivatives were also able to control the growth of the in vitro-derived bradyzoite forms of T. gondii EGS strain, causing its lysis and death. These findings promote the 1,10-phenanthroline derivatives as potential lead compounds for the development of a treatment for acute and chronic phases of toxoplasmosis.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: