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

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.

Keywords: :

• 1,10-phenanthroline
• antifungal resistance
• Candida species
• coordination compounds
• cytotoxicity
• metal complexes

Author contributions

Methodology: R Gandra, L Sangenito, C Pacheco, L Souza, P McCarron, M McCann and M Devereux; writing: R Gandra, L Ramos, M Branquinha and A Santos; supervision: M Branquinha and A Santos.

Financial disclosure

This study was supported by grants and fellowships from the Government of Ireland International Education Scholarships Programme; the Research Brazil Ireland (RBI) mobility initiative funded under the Science Foundation Ireland (SFI) International Strategic Cooperation Award (ISCA) Programme; and the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – financial code 001). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.