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Short Communication

Manganese(II), copper(II) and silver(I) complexes containing 1,10-phenanthroline/1,10-phenanthroline-5,6-dione against Candida species

    Rafael M Gandra

    Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    Programa de Pós-Graduação em Bioquímica (PPGBq), Instituto de Química (IQ), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

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    ,
    Clarissa A Pacheco

    Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

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    ,
    Leandro S Sangenito

    Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    Instituto Federal de Educação, Ciência e Tecnologia do Rio de Janeiro, Nilópolis, Rio de Janeiro, Brazil

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    ,
    Lívia S Ramos

    Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

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    ,
    Lucieri OP Souza

    Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

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    ,
    Pauraic McCarron

    Chemistry Department, Maynooth University, National University of Ireland, Maynooth, Ireland

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    ,
    Malachy McCann

    Chemistry Department, Maynooth University, National University of Ireland, Maynooth, Ireland

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    ,
    Michael Devereux

    The Centre for Biomimetic & Therapeutic Research, Focas Research Institute, Technological University Dublin, Dublin, Ireland

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    ,
    Marta H Branquinha

    Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    Rede Micologia RJ – Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil

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    &
    André LS Santos

    *Author for correspondence:

    E-mail Address: andre@micro.ufrj.br

    Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes (IMPG), Centro de Ciências da Saúde (CCS), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    Programa de Pós-Graduação em Bioquímica (PPGBq), Instituto de Química (IQ), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    Rede Micologia RJ – Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Rio de Janeiro, Brazil

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    Published Online:21 Feb 2024https://doi.org/10.2217/fmb-2023-0212

    Abstract

    Background: New chemotherapeutics are urgently required to treat Candida infections caused by drug-resistant strains. Methods: The effects of 16 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione/dicarboxylate complexed with Mn(II), Cu(II) and Ag(I) were evaluated against ten different Candida species. Results: Proliferation of Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis and Candida tropicalis was inhibited by three of six Cu(II) (MICs 1.52–21.55 μM), three of three Ag(I) (MICs 0.11–12.74 μM) and seven of seven Mn(II) (MICs 0.40–38.06 μM) complexes. Among these [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O, where oda = octanedioic acid, exhibited effective growth inhibition (MICs 0.4–3.25 μM), favorable activity indexes, low toxicity against Vero cells and good/excellent selectivity indexes (46.88–375). Conclusion: [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O represents a promising chemotherapeutic option for emerging, medically relevant and drug-resistant Candida species.

    Plain language summary

    Candida species are widespread fungi that can cause a variety of infections in humans, and some of them exhibit resistance profile to existing antifungal drugs. Consequently, it is imperative to discover novel treatments for these clinically relevant human infections. Complexes are chemical compounds containing metal ion components that are well-known for their antimicrobial properties, including antifungal activity. In the present study, we investigated the effects of 16 novel complexes against ten medically relevant Candida species, including some strains resistant to commonly used clinical antifungals. Our findings revealed that all complexes containing manganese and silver metals effectively inhibited the growth of all Candida species tested, albeit to varying extents. Some of these complexes exhibited superior antifungal activity and lower toxicity to mammalian cells compared to traditional antifungals, such as fluconazole. In conclusion, these new complexes hold promise as a potential novel approach for treating fungal infections, especially those caused by drug-resistant Candida strains.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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