Inhibitory action of phenothiazinium dyes against Neospora caninum

Autor(es)

Pereira, Luiz Miguel ^{[1, 2]} ; Mota, Caroline Martins ^[3] ; Baroni, Luciana ^[2] ; Bronzon da Costa, Cassia Mariana ^[2] ; Venancio Brochi, Jade Cabestre ^[2] ; Wainwright, Mark ^[4] ; Patriarca Mineo, Tiago Wilson ^[3] ; Leite Braga, Gilberto Ubida ^[2] ; Yatsuda, Ana Patricia ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Nucleo Apoio Pesquisa Prod Nat & Sintet, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Av Cafe Sn-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Uberlandia, Inst Biomed Sci, Dept Immunol, Uberlandia, MG - Brazil

^[4] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool L3 3AF, Merseyside - England

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 MAY 4 2020.
• Citações Web of Science: 0

Resumo

Neospora caninum is an Apicomplexan parasite related to important losses in livestock, causing abortions and decreased fertility in affected cows. Several chemotherapeutic strategies have been developed for disease control; however, no commercial treatment is available. Among the candidate drugs against neosporosis, phenothiazinium dyes, offer a low cost-efficient approach to parasite control. We report the anti-parasitic effects of the phenothiaziums Methylene Blue (MB), New Methylene Blue (NMB), 1,9-Dimethyl Methylene Blue (DMMB) and Toluidine Blue O (TBO) on N. caninum, using in vitro and in vivo models. The dyes inhibited parasite proliferation at nanomolar concentrations (0.019-1.83 mu M) and a synergistic effect was achieved when Methylene Blue was combined with New Methylene Blue (Combination Index = 0.84). Moreover, the phenothiazinium dyes improved parasite clearance when combined with Pyrimethamine (Pyr). Combination of Methylene Blue + 1,9-Dimethyl Methylene Blue demonstrated superior efficacy compared to Pyrimethamine based counterparts in an in vivo model of infection. We also observed that Methylene Blue, New Methylene Blue and 1,9-Dimethyl Methylene Blue increased by 5000% the reactive oxygen species (ROS) levels in N. caninum tachyzoites. Phenothiazinium dyes represent an accessible group of candidates with the potential to compound future formulations for neosporosis control. (AU)

• Processo FAPESP: 16/11386-5 - Estudo mecanístico da percepção e da resposta a luz visível no fungo entomopatogênico Metarhizium acridum
• Beneficiário: Gilberto Úbida Leite Braga
• Modalidade de apoio: Auxílio à Pesquisa - Regular