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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibitory action of phenothiazinium dyes against Neospora caninum

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Author(s):
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]
Total Authors: 9
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 10, n. 1 MAY 4 2020.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 16/11386-5 - Mechanistic study of perception and response to visible light in the entomopathogenic fungus Metarhizium acridum
Grantee:Gilberto Úbida Leite Braga
Support Opportunities: Regular Research Grants