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. 2024 Aug 23;14(3):289-295.
doi: 10.1556/1886.2024.00072. Print 2024 Sep 11.

Antifungal potential, mechanism of action, and toxicity of 1,4-naphthoquinone derivatives

Juan Diego Ribeiro de Almeida  1   2 , Raissa Sayumy Kataki Fonseca  1   2 , Naira Sulany Oliveira de Sousa  2 , Ana Cláudia Alves Cortez  2 , Emerson Silva Lima  3 , Juliana Gomes de Souza Oliveira  4 , Érica Simplício de Souza  1   5 , Hagen Frickmann  6   7 , João Vicente Braga de Souza  2
Affiliations

Antifungal potential, mechanism of action, and toxicity of 1,4-naphthoquinone derivatives

Juan Diego Ribeiro de Almeida et al. Eur J Microbiol Immunol (Bp). .

Abstract

Background: The rising prevalence of fungal infections and challenges such as adverse effects and resistance against existing antifungal agents have driven the exploration of new antifungal substances.

Methods: We specifically investigated naphthoquinones, known for their broad biological activities and promising antifungal capabilities. It specifically examined the effects of a particular naphthoquinone on the cellular components of Candida albicans ATCC 60193. The study also assessed cytotoxicity in MRC-5 cells, Artemia salina, and the seeds of tomatoes and arugula.

Results: Among four tested naphthoquinones, 2,3-DBNQ (2,3-dibromonaphthalene-1,4-dione) was identified as highly effective, showing potent antifungal activity at concentrations between 1.56 and 6.25 μg mL-1. However, its cytotoxicity in MRC-5 cells (IC50 = 15.44 µM), complete mortality in A. salina at 50 μg mL-1, and significant seed germination inhibition suggest limitations for its clinical use.

Conclusions: The findings indicate that primary antifungal mechanism of 2,3-DBNQ might involve disrupting fungal membrane permeability, which leads to increased nucleotide leakage. This insight underscores the need for further research to enhance the selectivity and safety of naphthoquinones for potential therapeutic applications.

Keywords: 2,3-DBNQ; antifungal potential; cytotoxicity; fungal membrane permeability; naphthoquinone derivatives.

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Conflict of interest statement

Funding sources: This work was supported by the Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM) for the funding of the research (EDITAL N. 010/2021- CT&I ÁREAS PRIORITÁRIAS and EDITAL N. 006/2019 – UNIVERSAL AMAZONAS and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) (Finance code 001).

Authors' Contributions: Contributions to the study were as follows: JDRA – study concept and design, investigation, analysis and interpretation of data, manuscript writing, statistical analysis; RSKF – validation of data, statistical analysis; NSOS – writing – review and editing; ACAC – validation of data; ESL – investigation; JGSO – investigation, writing – review and editing; JVBS – study concept and design, investigation, analysis and interpretation of data, manuscript writing, supervision, funding acquisition, approval of final version; ESS – writing – review and editing, formal analysis, supervision, approval of final version; HF – writing – review and editing, approval of final version.

Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be interpreted as a potential conflict of interest.

Figures

Fig. 1.
Fig. 1.
Naphthoquinones derived from 1,4-naphthoquinone investigated in the present study
Fig. 2.
Fig. 2.
Influence of exogenous ergosterol on the MIC (Minimum Inhibitory Concentration) of 2,3-DBNQ (2,3-dibromonaphthalene-1,4-dione) when applied with Candida albicans ATCC 60193. Axis X represents the two-folding concentrations of exogenous ergosterol in µg mL−1, while axis Y represents how many times the MIC value of the selected naphthoquinone against Candida albicans ATCC 60193 has been altered due to interaction with exogenous ergosterol. Amphotericin B its known for interact with ergosterol, as observed in the graph
Fig. 3.
Fig. 3.
Percentage of nucleotide extravasation in Candida albicans ATCC 60193 treated with 1× and 4× MIC (Minimum Inhibitory Concentration) of 2,3-DBNQ (2,3-dibromonaphthalene-1,4-dione). SDS (sodium dodecyl sulfate) 2% was used as positive control. Axis X represents the time of reading of the experiment in hours, while axis y represents the percentage of cell leakage detected in 260 nm caused by the selected naphthoquinone in Candida albicans ATCC 60193. As observed, when treated with 4× MIC value (25 μg mL−1) cell leakage rises up to 55.6% in 24 h
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References

    1. Ozturk I, Tunçel A, Yurt F, Biyiklioglu Z, Ince M, Ocakoglu K. Antifungal photodynamic activities of phthalocyanine derivatives on Candida albicans. Photodiagnosis Photodyn Ther. 2020;30:101715. - PubMed
    1. Hendrickson JA, Hu C, Aitken SL, Beyda N. Antifungal resistance: a concerning trend for the present and future. Curr Infect Dis Rep. 2019;21:1–8. - PubMed
    1. Harris E. CDC: Candida auris fungal infections and drug resistance on the rise. JAMA. 2023;329(15):1248–1248. - PubMed
    1. Chowdhary A, Prakash A, Sharma C, Kordalewska M, Kumar A, Sarma S, et al. . A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother. 2018;73(4):891–899. - PubMed
    1. Forsberg K, Woodworth K, Walters M, Berkow EL, Jackson B, Chiller T, et al. . Candida auris: the recent emergence of a multidrug-resistant fungal pathogen. Med Myco. 2019;57(1):1–12. - PubMed

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