Synergistic effects of in vitro combinations of piplartine, epiisopiloturine and praziquantel against Schistosoma mansoni.

Autor: Campelo YDM; Biodiversity and Biotechnology Research Center, Biotec, Federal University of Piauí, UFPI, Parnaíba, PI, 64202020, Brazil; Institute of Higher Education of Vale do Parnaíba, FAHESP/IESVAP, Parnaíba, PI, Brazil., Mafud AC; São Carlos Institute of Physics, University of São Paulo, São Carlos, SP, Brazil., Véras LMC; Biodiversity and Biotechnology Research Center, Biotec, Federal University of Piauí, UFPI, Parnaíba, PI, 64202020, Brazil., Guimarães MA; Biodiversity and Biotechnology Research Center, Biotec, Federal University of Piauí, UFPI, Parnaíba, PI, 64202020, Brazil; Phytobios Nordeste LTDA, Centroflora Group, Parnaíba, PI, Brazil., Yamaguchi LF; Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil., Lima DF; Biodiversity and Biotechnology Research Center, Biotec, Federal University of Piauí, UFPI, Parnaíba, PI, 64202020, Brazil; Federal University of Vale do São Francisco, Paulo Afonso, BA, Brazil., Arcanjo DDR; Biodiversity and Biotechnology Research Center, Biotec, Federal University of Piauí, UFPI, Parnaíba, PI, 64202020, Brazil., Kato MJ; Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil., Mendonça RZ; Laboratory of Parasitology, Butantan Institute, São Paulo, SP, Brazil., Pinto PLS; Enteroparasites Center, Adolfo Lutz Institute, São Paulo, SP, Brazil., Mascarenhas YP; São Carlos Institute of Physics, University of São Paulo, São Carlos, SP, Brazil., Silva MPN; Research Center for Neglected Diseases, Guarulhos University, Guarulhos, SP, Brazil., de Moraes J; Research Center for Neglected Diseases, Guarulhos University, Guarulhos, SP, Brazil., Eaton P; Biodiversity and Biotechnology Research Center, Biotec, Federal University of Piauí, UFPI, Parnaíba, PI, 64202020, Brazil; UCIBIO/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Portugal., de Souza de Almeida Leite JR; Biodiversity and Biotechnology Research Center, Biotec, Federal University of Piauí, UFPI, Parnaíba, PI, 64202020, Brazil; Faculty of Medicine, University of Brasilia, UnB, Brasília, DF, Brazil. Electronic address: jrsaleite@gmail.com.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2017 Apr; Vol. 88, pp. 488-499. Date of Electronic Publication: 2017 Jan 23.
DOI: 10.1016/j.biopha.2016.12.057
Abstrakt: Schistosomiasis is a world health problem, and praziquantel is the only drug currently used for the treatment. There is some evidence that extensive monotherapy of praziquantel may be leading to drug resistance in the parasite. In order to find alternative treatments, the effects of the combination of epiisopiloturine (EPI), piplartine (PPT) and praziquantel (PZQ) were evaluated. Similarity analysis of these compounds was performed using optimized molecular structures to compare the shape and the charge modeling of combinations between PZQ and EPI or PPT. Supported by this data, in vitro association of PZQ-PPT, PZQ-EPI, and EPI-PPT was carried out, and the activity of these combinations against Schistosoma mansoni was assessed. The results showed synergistic activity with a combination index (CI) of 0.42 for the treatment with PZQ-PPT. Both PZQ-EPI and EPI-PPT combinations also showed synergistic effects, with CI values of 0.86 and 0.61, respectively. Surface alterations in the tegument of adult schistosomes after the treatments were observed using laser confocal microscopy and scanning electron microscopy. Additionally, the association of EPI-PPT decreased the cytotoxicity when compared with both isolated compounds in three different lines of mammalian cells. Thus, synergistic combinations of PZQ-PPT, PZQ-EPI, and EPI-PPT create the possibility of reduced doses to be used against Schistosoma mansoni.
(Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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