title: Antifungal activity of 6-quinolinyl N-oxide chalcones against Paracoccidioides.
abstract: BACKGROUND
  Chalcones are an important class of natural compounds that have been widely applied as synthons in synthetic organic chemistry and possess diverse and interesting biological properties.
  
  
  METHODS
  We conducted tests with the synthetic substances 6-quinolinyl N-oxide chalcones 4c and 4e to determine their antifungal activity against several isolates of Paracoccidioides spp. and their activity in a murine model. We also determined whether the chalcones interacted with other drugs or interfered with the morphology of Paracoccidioides brasiliensis (Pb18) yeast cells.
  
  
  RESULTS
  We verified that the substances were active against Paracoccidioides spp., but we did not show an interaction with the drugs tested when only the fractional inhibitory concentration index values were considered individually. We observed that the substances induced in vitro morphological changes. Compounds 4c and 4e showed activity similar to itraconazole in treated mice, as demonstrated by their ability to reduce the number of cfu recovered from the lungs. Histopathological analysis showed that animals treated with 4c presented fewer areas containing inflammatory infiltrate and larger areas of preserved lung tissue, whereas animals treated with itraconazole showed accumulation of inflammatory infiltrate and some granulomas. Mice treated with 4e exhibited inflammation that compromised the tissue.
  
  
  CONCLUSIONS
  The results presented in this paper confirm the antifungal potential of the chalcones tested. The chalcone 4c was the more effective at controlling the disease in mice and this compound could be a candidate for future studies of the treatment of paracoccidioidomycosis.
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Nívea Pereira
authors.initials: NP
authors.lastname: de Sá
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Patrícia Silva
authors.initials: PS
authors.lastname: Cisalpino
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Luciana de Carvalho
authors.initials: Lde C
authors.lastname: Tavares
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Espíndola
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Moacir Geraldo
authors.initials: MG
authors.lastname: Pizzolatti
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Patrícia Campi
authors.initials: PC
authors.lastname: Santos
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Talles Prosperi
authors.initials: TP
authors.lastname: de Paula
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Carlos Augusto
authors.initials: CA
authors.lastname: Rosa
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Daniele da Glória
authors.initials: Dda G
authors.lastname: de Souza
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Daniel Assis
authors.initials: DA
authors.lastname: Santos
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil sjohann@icb.ufmg.br.
authors.forename: Susana
authors.initials: S
authors.lastname: Johann
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D006651:Histocytochemistry; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010087:Oxides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010228:Paracoccidioides / Q000187:drug effects*; D010229:Paracoccidioidomycosis / Q000188:drug therapy*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D047188:Chalcones; D010087:Oxides; D011804:Quinolines
keywords: morphological changes; murine model; paracoccidioidomycosis