New miconazole-based azoles derived from eugenol show activity against Candida spp. and Cryptococcus gattii by inhibiting the fungal ergosterol biosynthesis

Péret, Vinícius Augusto Campos; Reis, Rúbia Castro Fernandes Melo; Braga, Saulo Fehelberg Pinto; Benedetti, Monique Dias; Caldas, Ivo Santana; Carvalho, Diogo Teixeira; Santana, Luiz Felipe de Andrade; Johann, Susana; Souza, Thiago Belarmino de

doi:10.1016/j.ejmech.2023.115436

Cited by 8 publications

(2 citation statements)

References 17 publications

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“…Some studies have suggested that natural plant compounds affect important biofilm virulence factors, including the inhibition of biofilm formation, adhesion, promotion of biofilm cell detachment, and dispersion of established mature biofilms ( Lu et al., 2019 ; Park et al., 2019 ). Similar to classical antifungal drugs, these natural compounds exert anti- Candida effects by generating reactive oxygen species (ROS) and targeting Candida cellular metabolic pathways, including ABC transporter mediated drug efflux, cell cycle progression, mitochondrial activity, and ergosterol, chitin, and cell wall biosynthesis ( Shariati et al., 2022 ; Campos Péret et al., 2023 ).…”

Section: Introductionmentioning

confidence: 99%

Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall/membrane integrity and inducing apoptosis and autophagy

Qian,

Lu,

Gao

et al. 2024

Front. Cell. Infect. Microbiol.

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Isobavachalcone (IBC) is a natural flavonoid with multiple pharmacological properties. This study aimed to evaluate the efficacy of IBC against planktonic growth and biofilms of Candida albicans (C. albicans) and the mechanisms underlying its antifungal action. The cell membrane integrity, cell metabolic viability, and cell morphology of C. albicans treated with IBC were evaluated using CLSM and FESEM analyses. Crystal violet staining, CLSM, and FESEM were used to assess the inhibition of biofilm formation, as well as dispersal and killing effects of IBC on mature biofilms. RNA-seq combined with apoptosis and autophagy assays was used to examine the mechanisms underlying the antifungal action of IBC. IBC exhibited excellent antifungal activity with 8 μg/mL of MIC for C. albicans. IBC disrupted the cell membrane integrity, and inhibited biofilm formation. IBC dispersed mature biofilms and damaged biofilm cells of C. albicans at 32 μg/mL. Moreover, IBC induced apoptosis and autophagy-associated cell death of C. albicans. The RNA-seq analysis revealed upregulation or downregulation of key genes involved in cell wall synthesis (Wsc1 and Fks1), ergosterol biosynthesis (Erg3, and Erg11), apoptisis (Hsp90 and Aif1), as well as autophagy pathways (Atg8, Atg13, and Atg17), and so forth, in response to IBC, as evidenced by the experiment-based phenotypic analysis. These results suggest that IBC inhibits C. albicans growth by disrupting the cell wall/membrane, caused by the altered expression of genes associated with β-1,3-glucan and ergosterol biosynthesis. IBC induces apoptosis and autophagy-associated cell death by upregulating the expression of Hsp90, and altering autophagy-related genes involved in the formation of the Atg1 complex and the pre-autophagosomal structure. Together, our findings provide important insights into the potential multifunctional mechanism of action of IBC.

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Section: Introductionmentioning

confidence: 99%

Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall/membrane integrity and inducing apoptosis and autophagy

Qian,

Lu,

Gao

et al. 2024

Front. Cell. Infect. Microbiol.

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“…There are many literature studies showing the antifungal activities of imidazole and thiazole rings. 3–10 Antimycotic azoles exert antifungal activity by inhibiting lanosterol 14-alpha demethylase. The aim here is to prevent lanosterol demethylation.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel thiazol-2(3H)-imine derivatives as ergosterol biosynthesis inhibitors, and elucidation of their structures using a 2D NMR technique

Osmaniye,

Levent,

Sağlık

et al. 2023

New J. Chem.

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Recent advances in the synthesis of nitrogen-containing heterocyclic compounds via multicomponent reaction and their emerging biological applications: a review

Mallappa,

Chahar,

Choudhary

et al. 2024

J IRAN CHEM SOC

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New miconazole-based azoles derived from eugenol show activity against Candida spp. and Cryptococcus gattii by inhibiting the fungal ergosterol biosynthesis

Cited by 8 publications

References 17 publications

Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall/membrane integrity and inducing apoptosis and autophagy

Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall/membrane integrity and inducing apoptosis and autophagy

Synthesis of novel thiazol-2(3H)-imine derivatives as ergosterol biosynthesis inhibitors, and elucidation of their structures using a 2D NMR technique

Recent advances in the synthesis of nitrogen-containing heterocyclic compounds via multicomponent reaction and their emerging biological applications: a review

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