Glucosyl‐1,2,3‐triazoles derived from eugenol and analogues: Synthesis, anti‐<i>Candida</i> activity, and molecular modeling studies in CYP‐51

Magalhães, Lorena Severiano de; Reis, Adriana Cotta Cardoso; Nakao, Izadora Amaral; Péret, Vinícius Augusto Campos; Reis, Rúbia Castro Fernandes Melo; Silva, Naiara Chaves; Dias, Amanda Latércia Tranches; Carvalho, Diogo Teixeira; Dias, Danielle Ferreira; Brandão, Geraldo Célio; Braga, Saulo Fehelberg Pinto; Souza, Thiago Belarmino de

doi:10.1111/cbdd.13948

Cited by 10 publications

(4 citation statements)

References 25 publications

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“…Furthermore, in order to verify other possible mechanisms of action of chlorogenic acid, it was found that it exhibited promising affinity energy in the complex with CYP51, an enzyme involved in ergosterol synthesis and, therefore, essential for membrane stability and survival of the fungus [81], and with Yeast Cytochrome BC1 Complex. In a study carried out by [82] it was verified that the inhibition of cytochrome BC1 is related to the reduction of resistance to azoles, the impediment of the fungus' adaptation to nutrient deprivation, the sensitization of C. albicans to macrophage attack and reduced virulence.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the antifungal effect of chlorogenic acid against strains of Candida spp. resistant to fluconazole: apoptosis induction and in silico analysis of the possible mechanisms of action

Silva

Sá

Santos

et al. 2022

Journal of Medical Microbiology

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Introduction. Candida spp. are commensal fungal pathogens of humans, but when there is an imbalance in the microbiota, or weak host immunity, these yeasts can become pathogenic, generating high medical costs. Gap Statement. With the increase in resistance to conventional antifungals, the development of new therapeutic strategies is necessary. This study evaluated the in vitro antifungal activity of chlorogenic acid against fluconazole-resistant strains of Candida spp. Mechanism of action through flow cytometry and in silico analyses, as well as molecular docking assays with ALS3 and SAP5, important proteins in the pathogenesis of Candida albicans associated with the adhesion process and biofilm formation. Results. The chlorogenic acid showed in vitro antifungal activity against the strains tested, causing reduced cell viability, increased potential for mitochondrial depolarization and production of reactive oxygen species, DNA fragmentation and phosphatidylserine externalization, indicating an apoptotic process. Concerning the analysis through docking, the complexes formed between chlorogenic acid and the targets Thymidylate Kinase, CYP51, 1Yeast Cytochrome BC1 Complex e Exo-B-(1,3)-glucanase demonstrated more favourable binding energy. In addition, chlorogenic acid presented significant interactions with the ALS3 active site residues of C. albicans, important in the adhesion process and resistance to fluconazole. Regarding molecular docking with SAP5, no significant interactions were found between chlorogenic acid and the active site of the enzyme. Conclusion. We concluded that chlorogenic acid has potential use as an adjuvant in antifungal therapies, due to its anti-Candida activity and ability to interact with important drug targets.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the antifungal effect of chlorogenic acid against strains of Candida spp. resistant to fluconazole: apoptosis induction and in silico analysis of the possible mechanisms of action

Silva

Sá

Santos

et al. 2022

Journal of Medical Microbiology

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“…Some glucosyl‐1,2,3‐triazoles derived from eugenol and substituted phenols were synthesized by Magalhães et al. (2021). The peracetylated triazole hybrids I1 (a eugenol derivative) and I2 (a dihydroeugenol derivative) indicated the most promising antifungal activity against Candida krusei , with the IC 50 values of 26.1 and 25.98 μM, respectively.…”

Section: Antifungal 123‐triazole Hybridsmentioning

confidence: 99%

“…Acetyl groups play a key role in the antifungal activity of peracetylated compounds ( I1 ‐ I2 ) and probably might act as prodrugs, compared with their deacetylated forms. Molecular docking and molecular dynamics studies have revealed that the antifungal activity of some peracetylated triazole compounds might be due to the inhibition of 14α‐lanosterol demethylase and disruption of the fungal membrane (Magalhães et al., 2021).…”

Section: Antifungal 123‐triazole Hybridsmentioning

confidence: 99%

Click chemistry beyond metal‐catalyzed cycloaddition as a remarkable tool for green chemical synthesis of antifungal medications

Tahghighi,

Azerang

2024

Chem Biol Drug Des

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Click chemistry is widely used for the efficient synthesis of 1,4‐disubstituted‐1,2,3‐triazole, a well‐known scaffold with widespread biological activity in the pharmaceutical sciences. In recent years, this magic ring has attracted the attention of scientists for its potential in designing and synthesizing new antifungal agents. Despite scientific and medical advances, fungal infections still account for more than 1.5 million deaths globally per year, especially in people with compromised immune function. This increasing trend is definitely related to a raise in the incidence of fungal infections and prevalence of antifungal drug resistance. In this condition, an urgent need for new alternative antifungals is undeniable. By focusing on the main aspects of reaction conditions in click chemistry, this review was conducted to classify antifungal 1,4‐disubstituted‐1,2,3‐triazole hybrids based on their chemical structures and introduce the most effective triazole antifungal derivatives. It was notable that in all reactions studied, Cu(I) catalysts generated in situ by the reduction in Cu(II) salts or used copper(I) salts directly, as well as mixed solvents of t‐BuOH/H2O and DMF/H2O had most application in the synthesis of triazole ring. The most effective antifungal activity was also observed in fluconazole analogs containing 1,2,3‐triazole moiety and benzo‐fused five/six‐membered heterocyclic conjugates with a 1,2,3‐triazole ring, even with better activity than fluconazole. The findings of structure–activity relationship and molecular docking of antifungal derivatives synthesized with copper‐catalyzed azide–alkyne cycloaddition (CuAAC) could offer medicinal chemistry scientists valuable data on designing and synthesizing novel triazole antifungals with more potent biological activities in their future research.

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“…It displayed a wider range of biological activities than compound 39. Overall, the molecular modelling studies revealed that compounds 17 antifungal activity is attributed to the inhibition of CYP51, which prevents the formation of fungal ergosterol [110]. Pharmaceutics 2023, 15, x FOR PEER REVIEW 12 of 23…”

Section: Eugenolmentioning

confidence: 99%

Antifungal Activities of Natural Products and Their Hybrid Molecules

Khwaza,

Aderibigbe

2023

Pharmaceutics

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The increasing cases of drug resistance and high toxicity associated with the currently used antifungal agents are a worldwide public health concern. There is an urgent need to develop new antifungal drugs with unique target mechanisms. Plant-based compounds, such as carvacrol, eugenol, coumarin, cinnamaldehyde, curcumin, thymol, etc., have been explored for the development of promising antifungal agents due to their diverse biological activities, lack of toxicity, and availability. However, researchers around the world are unable to fully utilize the potential of natural products due to limitations, such as their poor bioavailability and aqueous solubility. The development of hybrid molecules containing natural products is a promising synthetic approach to overcome these limitations and control microbes’ capability to develop resistance. Based on the potential advantages of hybrid compounds containing natural products to improve antifungal activity, there have been different reported synthesized hybrid compounds. This paper reviews different literature to report the potential antifungal activities of hybrid compounds containing natural products.

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Glucosyl‐1,2,3‐triazoles derived from eugenol and analogues: Synthesis, anti‐Candida activity, and molecular modeling studies in CYP‐51

Abstract: This work describes the synthesis, anti-Candida, and molecular modeling studies of eighteen new glucosyl-1,2,3-triazoles derived from eugenol and correlated phenols. The new compounds were characterized by combined Fourier

Cited by 10 publications

References 25 publications

Evaluation of the antifungal effect of chlorogenic acid against strains of Candida spp. resistant to fluconazole: apoptosis induction and in silico analysis of the possible mechanisms of action

Evaluation of the antifungal effect of chlorogenic acid against strains of Candida spp. resistant to fluconazole: apoptosis induction and in silico analysis of the possible mechanisms of action

Click chemistry beyond metal‐catalyzed cycloaddition as a remarkable tool for green chemical synthesis of antifungal medications

Antifungal Activities of Natural Products and Their Hybrid Molecules

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