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.
Keywords: 1,10-phenanthroline; Candida species; antifungal resistance; coordination compounds; cytotoxicity; metal complexes.
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.