1,4-Naphthoquinone derivatives potently suppress Candida albicans growth, inhibit formation of hyphae and show no toxicity toward zebrafish embryos

Janeczko, Monika; Kubiński, Konrad; Martyna, Aleksandra; Muzyczka, Angelika; Boguszewska-Czubara, Anna; Czernik, S.; Tokarska-Rodak, Małgorzata; Chwedczuk, Marta; Demchuk, Oleg M.; Golczyk, Hieronim; Masłyk, Maciej

doi:10.1099/jmm.0.000700

Cited by 19 publications

(14 citation statements)

References 41 publications

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“…The obtained results show a slight increase in the crystal violet uptake (12%) by C. albicans cells when tested at the MIC concentration (Figure 2D). One of the 1,4-naphtoquinone derivatives tested recently caused higher uptake (31%, [6]) of the dye, which may suggest a different mechanism of 4-AN action that is not directly involved in cell membrane damage.…”

Section: Resultsmentioning

confidence: 99%

“…Compounds that arise from a quinone moiety containing an oxime group are reasonable alternatives. There are many reports on the antimycotic properties of both quinone derivatives and compounds substituted with oximes, including anti- Candida activity [5,6,7,8]. Very recently, strong anti- Candida activity (MIC = 4 µg/mL) of the arylcyanomethylenequinone oxime (4-AN) (Figure 1) connected with the inhibition of kinase activity has been revealed [9].…”

Section: Introductionmentioning

confidence: 99%

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The Anti-Candida albicans Agent 4-AN Inhibits Multiple Protein Kinases

et al. 2019

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Small molecules containing quinone and/or oxime moieties have been found as promising anti-fungal agents. One of them is 4-AN, a recently reported potent anti-Candida compound, which inhibits the formation of hyphae, decreases the level of cellular phosphoproteome, and finally shows no toxicity towards human erythrocytes and zebrafish embryos. Here, further research on 4-AN is presented. The results revealed that the compound: (i) Kills Candida clinical isolates, including these with developed antibiotic resistance, (ii) affects mature biofilm, and (iii) moderately disrupts membrane permeability. Atomic force microscopy studies revealed a slight influence of 4-AN on the cell surface architecture. 4-AN was also shown to inhibit multiple various protein kinases, a characteristic shared by most of the ATP-competitive inhibitors. The presented compound can be used in novel strategies in the fight against candidiasis, and reversible protein phosphorylation should be taken into consideration as a target in designing these strategies.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Anti-Candida albicans Agent 4-AN Inhibits Multiple Protein Kinases

et al. 2019

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“…9) improved the inhibition of biofilm formation by more than 60% with a better profile than the standard antibacterial drug, ciprofloxacin. 53,54) 1,4-Naphthoquinone derivatives were found to significantly affect some fungal strains and suppress various bacteria growth, hyphal formation and cell aggregation. 55) A series of novel, substituted 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones (30)(31)(32)(33)(34)(35)(36) (Fig.…”

Section: Cardioprotective and Anti-ischemic Propertiesmentioning

confidence: 99%

1,4-Naphthoquinones: Some Biological Properties and Application

2020

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Over the past decade, a number of new 1,4-naphthoquinones have been isolated from natural sources and new 1,4-naphthoquinones with diverse structural features have been synthesized. Cardioprotective, antiischemic, hepatoprotective, neuroprotective and some other new properties were found for these compounds; their role in protecting against neurodegenerative diseases has been established. Their anti-inflammatory, antimicrobial and antitumor activities have been studied in more detail; new, previously unknown intracellular molecular targets and mechanisms of action have been discovered. Some compounds of this class are already being used as a medicinal drugs and some substances can be used as biochemical tools and probes for non-invasive detection of pathological areas in cells and tissues in myocardial infarction and neurodegenerative diseases using modern molecular imaging techniques.

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“…One of approaches to solving this issue is to discover new agents that overcome cellular and molecular antifungal resistance. Since a large number of chemicals derived from quinones show antifungal properties, we focused our research on this class of chemicals [ 5 , 6 , 7 ]. The 4-AN is a recently revealed antifungal agent containing a quinone methide moiety substituted with an oxime group ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Antifungal Agent 4-AN Changes the Genome-Wide Expression Profile, Downregulates Virulence-Associated Genes and Induces Necrosis in Candida albicans Cells

et al. 2020

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In the light of the increasing occurrence of antifungal resistance, there is an urgent need to search for new therapeutic strategies to overcome this phenomenon. One of the applied approaches is the synthesis of small-molecule compounds showing antifungal properties. Here we present a continuation of the research on the recently discovered anti-Candida albicans agent 4-AN. Using next generation sequencing and transcriptional analysis, we revealed that the treatment of C. albicans with 4-AN can change the expression profile of a large number of genes. The highest upregulation was observed in the case of genes involved in cell stress, while the highest downregulation was shown for genes coding sugar transporters. Real-time PCR analysis revealed 4-AN mediated reduction of the relative expression of genes engaged in fungal virulence (ALS1, ALS3, BCR1, CPH1, ECE1, EFG1, HWP1, HYR1 and SAP1). The determination of the fractional inhibitory concentration index (FICI) showed that the combination of 4-AN with amphotericin B is synergistic. Finally, flow cytometry analysis revealed that the compound induces mainly necrosis in C. albicans cells.

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1,4-Naphthoquinone derivatives potently suppress Candida albicans growth, inhibit formation of hyphae and show no toxicity toward zebrafish embryos

Abstract: Our research has evidenced the effectiveness of 1,4-naphthoquinones as potential anti-Candida agents.

Cited by 19 publications

References 41 publications

The Anti-Candida albicans Agent 4-AN Inhibits Multiple Protein Kinases

The Anti-Candida albicans Agent 4-AN Inhibits Multiple Protein Kinases

1,4-Naphthoquinones: Some Biological Properties and Application

Antifungal Agent 4-AN Changes the Genome-Wide Expression Profile, Downregulates Virulence-Associated Genes and Induces Necrosis in Candida albicans Cells

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