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

IHMT

Instituto de Higiene e Medicina Tropical

  • O Instituto
    • Missão
    • Mensagem do Diretor
    • Órgãos de governo
    • Docentes e investigadores
    • Portal de Denúncias UNL
  • Ensino
    • Mestrados
    • Doutoramentos
    • Cursos de Especialização
    • Formação transversal
    • Cursos de Curta Duração
    • Ensino à Distância
    • Apoio ao Desenvolvimento
    • Serviços académicos
    • NOVA Open Academy
  • Investigação
    • Centro GHTM
    • Unidades de Ensino e de Investigação (UEI)
      • Unidade de Clínica Tropical
      • Unidade de Microbiologia Médica
      • Unidade de Parasitologia Médica
      • Unidade de Saúde Pública Global
      • Serviço de Apoio à Ciência e Comunidade
    • Biobanco
    • BLOODless
    • Centro Colaborador OMS
    • Publicações
  • Serviços e gestão
    • Biblioteca
    • Sistema de Qualidade
    • Estatutos e regulamentos
    • Plano de Atividades
    • Relatório de Atividades
    • Relatório de Gestão
    • Contratos públicos
    • Recursos humanos
      • Concursos e bolsas
        • Concursos – Docentes e Investigadores
        • Concursos – Não Docentes e Não Investigadores
        • Bolsas de Investigação
      • Contratos
      • Avaliação de Desempenho
        • Ciclo Avaliativo
          • Biénio 2021-2022
          • Biénio 2023-2024
        • Conselho Coordenador de Avaliação
        • Comissão Paritária
      • Mobilidade
      • Listas Nominativas
  • Doenças Tropicais
    • Consulta do Viajante
    • Dossiês Informativos
    • Glossário
    • Museu
    • Vídeos
    • MosquitoWeb
  • Comunidade
    • Cooperação e Desenvolvimento
    • Formação
    • Parcerias
  • Contactos
  • Candidaturas
  • pt
    • pt
    • en
Home / Publicações / Synthesis, structural characterization and leishmanicidal activity evaluation of ferrocenyl N-heterocyclic compounds

Synthesis, structural characterization and leishmanicidal activity evaluation of ferrocenyl N-heterocyclic compounds

  • Autores: Campino L, Helena Garcia M, Madureira J, Maia C, Marques M, Matos CP, Morais TS, Paula Robalo M, Piedade MFM, Quintal S, Villa De Brito MJ
  • Ano de Publicação: 2013
  • Journal: Journal of Organometallic Chemistry
  • Link: http://www.sciencedirect.com/science/article/pii/S0022328X13005512

New ferrocenyl derivatives with the general formula FcC(O)L [Fc = (η5-C5H5)Fe(η5-C5H4)], where L is an aminoquinoline or hydroxyaminoquinoline, have been synthesized for evaluation of their leishmanicidal properties. The compounds were designed with ferrocene coupled to the quinolines by an amide or ester bridge. Ferrocenyl component is intended to act as quinoline carrier and ROS producer after in vivo oxidation to Fe(III), while decreasing normal cell cytotoxicity of coupled quinolines. The bridge was chosen based on its known ability to undergo hydrolysis by the protease/esterase rich media in phagolysosomes, the target of the intracellular form of leishmania parasites.

The new compounds include N-(quinolin-3-yl)ferrocenamide (4), N-(quinolin-5-yl)ferrocenamide (5), N-(quinolin-6-yl)ferrocenamide (6), N-(2-methyl-quinolin-4-yl)ferrocenamide (7), N-(2-methylquinolin-6-yl)ferrocenamide (8), N-(6-methoxy-quinolin-8-yl)ferrocenamide (9), 2-amino-quinolin-8-yl ferrocenoate (10) and 2-amino-quinolin-4-yl ferrocenoate (11). They were characterized by NMR, cyclic voltammetry, mass spectrometry, UV/vis, FT-IR and elemental analysis, which confirmed all the proposed molecular structures. Compounds 7 and 8 were also structurally characterized by single crystal X-ray diffraction. In 7, the 4-amino-2-methylquinoline moiety is perpendicular to the substituted cyclopentadienyl ring (Cp), while in 8 the 6-amino-2-methylquinoline component is coplanar to the substituted Cp.

The new compounds (4–11), same as four other previously published (1-ferrocenoyl-1H-(2-aminobenzimidazole) (1), 1-ferrocenoyl-1H-benzimidazole (2), 1-ferrocenoyl-1H-imidazole (3) and N-(pyridin-4-yl)ferrocenamide (12)), were evaluated in vitro in cultures of a Leishmania infantum strain, isolated from a human visceral leishmaniasis case, to establish their leishmanicidal activity. The toxicity against the human caucasian histiocytic lymphoma U-937 cell line was analyzed for the same set of compounds. All of them show activity against promastigote forms of L. infantum parasites at relatively high concentration (64–269 μM). Among the complexes that showed a better ratio between the toxic and the therapeutic dose, 3, 9 and 12 were selected for further studies in infected macrophages. Such compounds showed a very significant increase in their activity (17–23 times) giving very similar IC50 values (5.2–5.7 μM). All three compounds gave significantly better therapeutic indexes (88.5, 12; 56.4, 3; 16.6, 9) than the control miltefosine (6.1). 2

Synthesis, structural characterization and leishmanicidal activity evaluation of ferrocenyl N-heterocyclic compounds

  • Autores: Campino L, Helena Garcia M, Madureira J, Maia C, Marques M, Matos CP, Morais TS, Paula Robalo M, Piedade MFM, Quintal S, Villa De Brito MJ
  • Ano de Publicação: 2013
  • Journal: Journal of Organometallic Chemistry
  • Link: http://www.sciencedirect.com/science/article/pii/S0022328X13005512

New ferrocenyl derivatives with the general formula FcC(O)L [Fc = (η5-C5H5)Fe(η5-C5H4)], where L is an aminoquinoline or hydroxyaminoquinoline, have been synthesized for evaluation of their leishmanicidal properties. The compounds were designed with ferrocene coupled to the quinolines by an amide or ester bridge. Ferrocenyl component is intended to act as quinoline carrier and ROS producer after in vivo oxidation to Fe(III), while decreasing normal cell cytotoxicity of coupled quinolines. The bridge was chosen based on its known ability to undergo hydrolysis by the protease/esterase rich media in phagolysosomes, the target of the intracellular form of leishmania parasites.

The new compounds include N-(quinolin-3-yl)ferrocenamide (4), N-(quinolin-5-yl)ferrocenamide (5), N-(quinolin-6-yl)ferrocenamide (6), N-(2-methyl-quinolin-4-yl)ferrocenamide (7), N-(2-methylquinolin-6-yl)ferrocenamide (8), N-(6-methoxy-quinolin-8-yl)ferrocenamide (9), 2-amino-quinolin-8-yl ferrocenoate (10) and 2-amino-quinolin-4-yl ferrocenoate (11). They were characterized by NMR, cyclic voltammetry, mass spectrometry, UV/vis, FT-IR and elemental analysis, which confirmed all the proposed molecular structures. Compounds 7 and 8 were also structurally characterized by single crystal X-ray diffraction. In 7, the 4-amino-2-methylquinoline moiety is perpendicular to the substituted cyclopentadienyl ring (Cp), while in 8 the 6-amino-2-methylquinoline component is coplanar to the substituted Cp.

The new compounds (4–11), same as four other previously published (1-ferrocenoyl-1H-(2-aminobenzimidazole) (1), 1-ferrocenoyl-1H-benzimidazole (2), 1-ferrocenoyl-1H-imidazole (3) and N-(pyridin-4-yl)ferrocenamide (12)), were evaluated in vitro in cultures of a Leishmania infantum strain, isolated from a human visceral leishmaniasis case, to establish their leishmanicidal activity. The toxicity against the human caucasian histiocytic lymphoma U-937 cell line was analyzed for the same set of compounds. All of them show activity against promastigote forms of L. infantum parasites at relatively high concentration (64–269 μM). Among the complexes that showed a better ratio between the toxic and the therapeutic dose, 3, 9 and 12 were selected for further studies in infected macrophages. Such compounds showed a very significant increase in their activity (17–23 times) giving very similar IC50 values (5.2–5.7 μM). All three compounds gave significantly better therapeutic indexes (88.5, 12; 56.4, 3; 16.6, 9) than the control miltefosine (6.1). 2

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
  • Portal de Denúncias UNL

NOVA University of Lisbon Logo

Siga-nos

  • Facebook
  • Instagram
  • LinkedIn
  • Twitter
  • YouTube

Receber a “newsletter”

© Copyright 2025 IHMT-UNL Todos os Direitos Reservados.
  • Universidade Nova de Lisboa
  • Fundação para a Ciência e a Tecnologia

    UIDB/04413/2020
    UIDP/04413/2020

We use cookies to ensure that we give you the best experience on our website. If you continue to use this site we will assume that you are happy with it.Ok