• Skip to primary navigation
  • Skip to main content
  • Skip to footer
  • Pessoal
    • Webmail
    • Área de Docentes
    • Área de Não-Docentes
  • Estudantes
    • Webmail
    • Moodle
    • NetP@
    • Biblioteca
    • Escola Doutoral
    • Serviços Académicos
    • Trabalhar no IHMT

IHMT

Instituto de Higiene e Medicina Tropical

  • O Instituto
    • Missão
    • História
    • Mensagem do Diretor
    • Órgãos de governo
    • Docentes e investigadores
    • Unidades de Ensino e de Investigação
  • Ensino
    • Doutoramentos
    • Mestrados
    • Cursos de Especialização
    • Formação transversal
    • Cursos de Curta Duração
    • Ensino à Distância
    • Apoio ao Desenvolvimento
    • Serviços académicos
  • Investigação
    • Centro GHTM
    • Unidade de Clínica Tropical
    • Unidade de Microbiologia Médica
    • Unidade de Parasitologia Médica
    • Unidade de Saúde Pública Global
    • Serviço de Interesse Comum
    • Biobanco
    • Centro Colaborador da OMS
    • Publicações
  • Serviços e gestão
    • Biblioteca
    • Sistema de Qualidade
    • Estatutos e regulamentos
    • Relatórios
    • Contratos públicos
    • Recursos humanos
      • Concursos e bolsas
      • Contratos
      • Avaliação e Desempenho
        • Processo Eleitoral da Comissão Paritária
      • Mobilidade
  • Doenças Tropicais
    • Consulta do Viajante
    • Glossário
    • Museu
    • Vídeos
    • MosquitoWeb
  • Comunidade
    • Cooperação e Desenvolvimento
    • Formação
    • Parcerias
  • Contactos
  • Português
  • English
Home / Publicações / Probing the aurone scaffold against Plasmodium falciparum: Design, synthesis and antimalarial activity

Probing the aurone scaffold against Plasmodium falciparum: Design, synthesis and antimalarial activity

  • Autores: Carrasco MP, dos Santos DJVA, Gois A, Gonçalves L, Guedes RC, Gut J, Haenscheid T, Machado M, Moreira R, Newton AS, Nogueira F, Rosenthal PJ
  • Ano de Publicação: 2014
  • Journal: European Journal of Medicinal Chemistry
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/24813880

A library comprising 44 diversely substituted aurones derivatives was synthesized by straightforward aldol condensation reactions of benzofuranones and the appropriately substituted benzaldehydes. Microwave enhanced synthesis using palladium catalyzed protocols was introduced as a powerful strategy for extending the chemical space around the aurone scaffold. Additionally, Mannich-base derivatives, containing a 7-aminomethyl-6-hydroxy substitution pattern at ring A, were also prepared. Screening against the chloroquine resistant Plasmodium falciparum W2 strain identified novel aurones with IC50 values in the low micromolar range. The most potent compounds contained a basic moiety, with the ability to accumulate in acidic digestive vacuole of the malaria parasite. However, none of those aurones revealed significant activity against hemozoin formation and falcipain-2, two validated targets expressed during the blood stage of P. falciparum infection and functional in digestive vacuole of the parasite. Overall, this study highlight (i) the usefulness of aurones as platforms for synthetic procedures using palladium catalyzed protocols to rapidly deliver lead compounds for further optimization and (ii) the potential of novel aurone derivatives as promising antimalarial compounds.

Probing the aurone scaffold against Plasmodium falciparum: Design, synthesis and antimalarial activity

  • Autores: Carrasco MP, dos Santos DJVA, Gois A, Gonçalves L, Guedes RC, Gut J, Haenscheid T, Machado M, Moreira R, Newton AS, Nogueira F, Rosenthal PJ
  • Ano de Publicação: 2014
  • Journal: European Journal of Medicinal Chemistry
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/24813880

A library comprising 44 diversely substituted aurones derivatives was synthesized by straightforward aldol condensation reactions of benzofuranones and the appropriately substituted benzaldehydes. Microwave enhanced synthesis using palladium catalyzed protocols was introduced as a powerful strategy for extending the chemical space around the aurone scaffold. Additionally, Mannich-base derivatives, containing a 7-aminomethyl-6-hydroxy substitution pattern at ring A, were also prepared. Screening against the chloroquine resistant Plasmodium falciparum W2 strain identified novel aurones with IC50 values in the low micromolar range. The most potent compounds contained a basic moiety, with the ability to accumulate in acidic digestive vacuole of the malaria parasite. However, none of those aurones revealed significant activity against hemozoin formation and falcipain-2, two validated targets expressed during the blood stage of P. falciparum infection and functional in digestive vacuole of the parasite. Overall, this study highlight (i) the usefulness of aurones as platforms for synthetic procedures using palladium catalyzed protocols to rapidly deliver lead compounds for further optimization and (ii) the potential of novel aurone derivatives as promising antimalarial compounds.

Footer

INSTITUTO DE HIGIENE E
MEDICINA TROPICAL
UNIVERSIDADE NOVA DE LISBOA
Rua da Junqueira, 100 1349-008 Lisboa
T +351 213 652 600
geral@ihmt.unl.pt

Consulta do Viajante e Medicina Tropical
T +351 213 652 630
T +351 213 652 690
T +351 91 182 37 48
T +351 91 182 44 67
medicina.viagens@ihmt.unl.pt

Ensino
Investigação
Medicina Tropical
Cooperação

Siga-nos

  • Facebook
  • LinkedIn
  • YouTube

Receber a “newsletter”

© Copyright 2023 IHMT-UNL Todos os Direitos Reservados.
  • Universidade Nova de Lisboa
  • Fundação para a Ciência e a Tecnologia

    Project UID/Multi/04413/2013