Antifungal potential of the new copper(II)-theophylline/1,10-phenanthroline complex against drug-resistant Candida species

Frota, Heloisa F.; Lorentino, Carolline M. A.; Barbosa, Pedro F.; Ramos, Lívia S.; Barcellos, Iuri C.; Giovanini, Lucas; Souza, Lucieri O. P.; Oliveira, Simone S. C.; Abosede, Olufunso O.; Ogunlaja, Adeniyi S.; Pereira, Matheus M.; Branquinha, Marta H.; Santos, André L. S.

doi:10.1007/s10534-023-00549-y

Cited by 3 publications

(4 citation statements)

References 59 publications

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“…These same NACs were also employed in a previous published paper that described the antifungal action of the compound CTP (Frota et al 2023). Furthermore, the observed resistance pro les of these NACs to standard antifungals are as follows: C. auris (from blood), C. haemulonii (from foot sole) and C. krusei (from gastrostomy) exhibited resistance to both uconazole and amphotericin B; while C. glabrata (from gastrostomy), C. parapsilosis (from gastrostomy) and C. tropicalis (from gastrostomy) displayed resistance to uconazole but remain susceptible to amphotericin B (Frota et al 2023). The fungal cells were cultured in Sabouraud-dextrose broth (SAB; containing 2% glucose, 1% peptone, and 0.5% yeast extract) at 37°C with constant stirring at 200 rpm for 48 h. Growth was evaluated by enumerating yeast cells using a Neubauer chamber.…”

Section: Yeasts and Growth Conditionsmentioning

confidence: 99%

“…The present study utilized six clinical isolates of various NACs (C. auris, C. glabrata, C. haemulonii, C. krusei, C. parapsilosis and C. tropicalis) sourced from the mycotheque of the Laboratory for Advanced Studies on Emerging and Resistant Microorganisms (LEAMER; Microbiology Institute Paulo de Góes, Federal University of Rio de Janeiro, Brazil). These same NACs were also employed in a previous published paper that described the antifungal action of the compound CTP (Frota et al 2023). Furthermore, the observed resistance pro les of these NACs to standard antifungals are as follows: C. auris (from blood), C. haemulonii (from foot sole) and C. krusei (from gastrostomy) exhibited resistance to both uconazole and amphotericin B; while C. glabrata (from gastrostomy), C. parapsilosis (from gastrostomy) and C. tropicalis (from gastrostomy) displayed resistance to uconazole but remain susceptible to amphotericin B (Frota et al 2023).…”

Section: Yeasts and Growth Conditionsmentioning

confidence: 99%

“…Recently, our group reported on the anti-Candida activity of the copper(II)-theophylline/1,10-phenanthroline complex, called CTP -Cu(theo) 2 phen(H 2 O)•5H 2 O (Fig. 1), against uconazole and amphotericin-resistant isolates (Frota et al 2023).…”

Section: Introductionmentioning

confidence: 99%

“…Given the promising antifungal activity of the compound CTP (Frota et al 2023), coupled with the imperative need for the development of new chemotherapeutic options for the treatment of infections caused by NACs, in the present study, we have chosen to evaluate the effects of CTP on aspects of fungal cellular biology in medically relevant NACs in order to decipher its mechanisms of antifungal action.…”

Section: Introductionmentioning

confidence: 99%

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Unveiling the Antifungal Mechanisms of CTP, a New Copper(II)- Theophylline/1,10-Phenanthroline Complex, on Drug-Resistant Non-albicans Candida Species

Frota,

Barbosa,

Lorentino

et al. 2024

Preprint

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Candida species are the commonest opportunistic human fungal pathogens worldwide, with Candida albicans serving as the primary representative. However, non-albicans Candida species (NACs) have been on the rise in terms of incidence, and they are associated with outbreaks and instances of antifungal resistance. The search for new strategies to combat antifungal-resistant Candida strains is of paramount importance. Recently, our group reported the anti-Candida activity of a coordination compound containing copper(II) complexed with theophylline (theo) and 1,10-phenanthroline (phen), known as “CTP” – Cu(theo)2phen(H2O).5H2O. In the present work, we investigated the mechanisms of action of CTP against six medically relevant, antifungal-resistant NACs, including C. auris, C. glabrata, C. haemulonii, C. krusei, C. parapsilosis and C. tropicalis. CTP effectively inhibited the activity of mitochondrial dehydrogenases, leading to an increase in intracellular reactive oxygen species production. CTP treatment resulted in significant damage to the plasma membrane, as evidenced by the passive incorporation of propidium iodide, and DNA fragmentation as evidenced by the TUNEL assay. Scanning electron microscopy images confirmed that the fungal surface underwent substantial alterations due to CTP treatment, including the formation of invaginations that led to cavitations and lysis. These surface modifications significantly impacted the ability of Candida cells to adhere to the polystyrene surface and form a robust biofilm structure. Moreover, CTP was effective in disassembling mature biofilms formed by these NACs. CTP represents a promising avenue for the development of novel antifungals with innovative mechanisms of action against clinically relevant NACs that are resistant to antifungals commonly used in clinical settings.

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Section: Yeasts and Growth Conditionsmentioning

confidence: 99%

Section: Yeasts and Growth Conditionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Unveiling the Antifungal Mechanisms of CTP, a New Copper(II)- Theophylline/1,10-Phenanthroline Complex, on Drug-Resistant Non-albicans Candida Species

Frota,

Barbosa,

Lorentino

et al. 2024

Preprint

Self Cite

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show abstract

Unveiling the antifungal mechanisms of CTP, a new copper(II)-theophylline/1,10-phenanthroline complex, on drug-resistant non-albicans Candida species

Frota,

Barbosa,

Lorentino

et al. 2024

Biometals

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

Gandra,

Pacheco,

Sangenito

et al. 2024

Future Microbiol.

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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.

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Antifungal potential of the new copper(II)-theophylline/1,10-phenanthroline complex against drug-resistant Candida species

Cited by 3 publications

References 59 publications

Unveiling the Antifungal Mechanisms of CTP, a New Copper(II)- Theophylline/1,10-Phenanthroline Complex, on Drug-Resistant Non-albicans Candida Species

Unveiling the Antifungal Mechanisms of CTP, a New Copper(II)- Theophylline/1,10-Phenanthroline Complex, on Drug-Resistant Non-albicans Candida Species

Unveiling the antifungal mechanisms of CTP, a new copper(II)-theophylline/1,10-phenanthroline complex, on drug-resistant non-albicans Candida species

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

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