MARIA CRISTINA CARVALHO DO ESPIRITO SANTO

(Fonte: Lattes)
Índice h a partir de 2011
9
Lattes
Projetos de Pesquisa
Unidades Organizacionais
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses, Hospital das Clínicas, Faculdade de Medicina

Filtros

Limpar filtros

Configurações

search.filters.applied.f.dateIssued: 2021 ×

Resultados de Busca

Agora exibindo 1 - 2 de 2
  • article 15 Citação(ões) na Scopus
    Pyrazoline derivatives as promising novel antischistosomal agents
    (2021) MORAIS, Cristiane S.; MENGARDA, Ana C.; MIGUEL, Fabio B.; ENES, Karine B.; RODRIGUES, Vinicius C.; ESPIRITO-SANTO, Maria Cristina C.; SIYADATPANAH, Abolghasem; WILAIRATANA, Polrat; COURI, Mara R. C.; MORAES, Josue de
    Praziquantel is the only available drug to treat schistosomiasis, a parasitic disease that currently infects more than 240 million people globally. Due to increasing concerns about resistance and inadequate efficacy there is a need for new therapeutics. In this study, a series of 17 pyrazolines (15-31) and three pyrazoles (32-34) were synthesized and evaluated for their antiparasitic properties against ex vivo adult Schistosoma mansoni worms. Of the 20 compounds tested, six had a 50% effective concentration (EC50) below 30 mu M. Our best hit, pyrazoline 22, showed promising activity against adult schistosomes, with an EC50 < 10 mu M. Additionally, compound 22 had low cytotoxicity, with selectivity index of 21.6 and 32.2 for monkey and human cell lines, respectively. All active pyrazolines demonstrated a negative effect on schistosome fecundity, with a marked reduction in the number of eggs. Structure-activity relationship analysis showed that the presence of the non-aromatic heterocycle and N-substitution are fundamental to the antischistosomal properties. Pharmacokinetics, drug-likeness and medicinal chemistry friendliness studies were performed, and predicted values demonstrated an excellent drug-likeness profile for pyrazolines as well as an adherence to major pharmaceutical companies' filters. Collectively, this study demonstrates that pyrazoline derivatives are promising scaffolds in the discovery of novel antischistosomal agents.
  • article 4 Citação(ões) na Scopus
    Efficacy of carvacryl acetate in vitro and following oral administration to mice harboring either prepatent or patent Schistosoma mansoni infections
    (2021) SILVA, Bianca C.; MENGARDA, Ana C.; RODRIGUES, Vinicius C.; CAJAS, Rayssa A.; CARNAUBA, Paulo U.; ESPIRITO-SANTO, Maria Cristina C.; BEZERRA-FILHO, Carlos S. M.; SOUSA, Damiao P. de; MORAES, Josue de
    Schistosomiasis is a major public health problem that afflicts more than 240 million individuals globally, particularly in poor communities. Treatment of schistosomiasis relies heavily on a single oral drug, praziquantel, and there is interest in the search for new antischistosomal drugs. This study reports the anthelmintic evaluation of carvacryl acetate, a derivative of the terpene carvacrol, against Schistosoma mansoni ex vivo and in a schistosomiasis animal model harboring either adult (patent infection) or juvenile (prepatent infection) parasites. For comparison, data obtained with gold standard antischistosomal drug praziquantel are also presented. Initially in vitro effective concentrations of 50% (EC50) and 90% (EC90) were determined against larval and adult stages of S. mansoni. In an animal with patent infection, a single oral dose of carvacryl acetate (100, 200, or 400 mg/kg) caused a significant reduction in worm burden (30-40%). S. mansoni egg production, a process responsible for both life cycle and pathogenesis, was also markedly reduced (70-80%). Similar to praziquantel, carvacryl acetate 400 mg/kg had low efficacy in pre-patent infection. In tandem, although carvacryl acetate had interesting in vitro schistosomicidal activity, the compound exhibited low efficacy in terms of reduction of worm load in S. mansoni-infected mice.