Introductory Chapter: Azoles, Their Importance, and Applications

Kuznetsov, Aleksey E.

doi:10.5772/intechopen.98426

Cited by 7 publications

(5 citation statements)

References 50 publications

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“…Azole-based compounds have proved to be a very good source of medicinal agents. Various properties associated with these fragments include antimicrobial, anticancer, antihypertensive, anthelmintic, anti-HIV, anti-inflammatory, analgesic, anticonvulsant, sedative and other pharmacological activities [30]. Therefore, the synthesis of the mentioned compounds is attractive for researches interested in drug discovery and design.…”

Section: Synthesismentioning

confidence: 99%

Synthesis and investigation of antibacterial activity of 1-(4-substituted phenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives

Plaga,

Sapijanskaitė-Banevič,

Vaickelionienė

2023

chemija

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Hydrazides are very important precursors for the synthesis of a wide variety of derivatives, including heterocyclic compounds of biological interest in drug design and discovery. Acid hydrazides with a pyrrole, thiophene, furan, quinoline, isoquinoline, isoxazole and benzimidazole core in the structure were found to be used in medicine, pharmacy, agriculture and many other fields. In the search for compounds with antibacterial properties, mono- and dihydrazides were used in this study to prepare 1-(4-substituted phenyl)-5-oxopyr-rolidine-3-carbohydrazide derivatives bearing the corresponding hydrazone and azole substituents. The formation of the target compounds was performed via condensation reactions with the chosen aromatic aldehydes and isatin, which led to the construction of the appropriate hydrazone-type structures as well as with diketones which afforded compounds with pyrazole and pyrrole nuclei. In addition, a preliminary antibacterial evaluation of the synthesised compounds was performed using the gram-positive Bacillus subtilis and the gramnegative Escherichia coli bacterial strains. As it was expected, the evaluation revealed potential antibacterial candidates that can help address the global challenges of antibiotic resistance and infectious disease outbreaks.

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Section: Synthesismentioning

confidence: 99%

Synthesis and investigation of antibacterial activity of 1-(4-substituted phenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives

Plaga,

Sapijanskaitė-Banevič,

Vaickelionienė

2023

chemija

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“…Treatment of Candida infection (candidiasis) is unfortunately limited to 4 major classes of antifungal drugs: echinocandins, azoles, polyenes, and flucytosines. Echinocandins, such as caspofungin, target the fungal cell wall by inhibiting the synthesis of the carbohydrate β-1,3-glucan ( Balashov et al 2006 ; Lee et al 2012 ), while azoles, such as fluconazole and miconazole, inhibit the synthesis of ergosterol, thereby compromising the lipid composition of fungal membranes ( Kuznetsov 2021 ). Azoles specifically inhibit the 14α-demethylase, encoded by the C. albicans ERG11 gene, in the ergosterol synthesis pathway.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary diversity of the control of the azole response by Tra1 across yeast species

Librais,

Jiang,

Razzaq

et al. 2023

G3: Genes, Genomes, Genetics

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Tra1 is an essential co-activator protein of the yeast SAGA and NuA4 acetyltransferase complexes that regulate gene expression through multiple mechanisms including the acetylation of histone proteins. Tra1 is a pseudokinase of the PIKK family characterized by a C-terminal PI3K domain with no known kinase activity. However, mutations of specific arginine residues to glutamine in the PI3K domains (an allele termed tra1Q3) result in reduced growth and increased sensitivity to multiple stresses. In the opportunistic fungal pathogen Candida albicans, the tra1Q3 allele reduces pathogenicity and increases sensitivity to the echinocandin antifungal drug caspofungin, which disrupts the fungal cell wall. Here, we found that compromised Tra1 function, in contrast to what is seen with caspofungin, increases tolerance to the azole class of antifungal drugs, which inhibits ergosterol synthesis. In C. albicans, tra1Q3 increases expression of genes linked to azole resistance, such as ERG11 and CDR1. CDR1 encodes a multidrug ABC transporter associated with efflux of multiple xenobiotics, including azoles. Consequently, cells carrying tra1Q3 show reduced intracellular accumulation of fluconazole. In contrast, a tra1Q3 S. cerevisiae strain displayed opposite phenotypes: decreased tolerance to azole, decreased expression of the efflux pump PDR5 and increased intracellular accumulation of fluconazole. Therefore, our data provide evidence that Tra1 differentially regulates the antifungal response across yeast species.

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“…2006; Lee et al . 2012), while azoles, such as fluconazole and miconazole, inhibit the synthesis of ergosterol, thereby compromising the lipid composition of fungal membranes (Kuznetsov 2021). Azoles specifically inhibit the 14α-demethylase, encoded by the C. albicans ERG11 gene, in the ergosterol synthesis pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Treatment of Candida infection (candidiasis) is unfortunately limited to four major classes of antifungal drugs: echinocandins, azoles, polyenes and flucytosines. Echinocandins, such as caspofungin, target the fungal cell wall by inhibiting the synthesis of the carbohydrate β-1,3-glucan (Balashov et al 2006;Lee et al 2012), while azoles, such as fluconazole and miconazole, inhibit the synthesis of ergosterol, thereby compromising the lipid composition of fungal membranes (Kuznetsov 2021). Azoles specifically inhibit the 14αdemethylase, encoded by the C. albicans ERG11 gene, in the ergosterol synthesis pathway.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary diversity of the control of the azole response by Tra1 across yeast species

Nunes Librais,

Jiang,

Razzaq

et al. 2023

Preprint

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Tra1 is an essential co-activator protein of the yeast SAGA and NuA4 acetyltransferase complexes that regulate gene expression through multiple mechanisms including the acetylation of histone proteins. Tra1 is a pseudokinase of the PIKK family characterized by a C-terminal PI3K domain with no known kinase activity. However, mutations of specific arginine residues to glutamine in the PI3K domains (an allele termedtra1Q3) result in reduced growth and increased sensitivity to multiple stresses. In the opportunistic fungal pathogenCandida albicans, thetra1Q3allele reduces pathogenicity and increases sensitivity to the echinocandin antifungal drug caspofungin, which disrupts the fungal cell wall. Here, we found that loss of Tra1 function, in contrast to what is seen with caspofungin, increases tolerance to the azole class of antifungal drugs, which inhibits ergosterol synthesis. InC. albicans, tra1Q3increases expression of genes linked to azole resistance, such asERG11andCDR1. CDR1encodes a multidrug ABC transporter associated with efflux of multiple xenobiotics, including azoles. Consequently, cells carryingtra1Q3show reduced intracellular accumulation of fluconazole. In contrast, atra1Q3S. cerevisiaestrain displayed opposite phenotypes: decreased tolerance to azole, decreased expression of the efflux pumpPDR5and increased intracellular accumulation of fluconazole. Therefore, our data provide evidence that Tra1 differentially regulates the antifungal response across yeast species.

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Introductory Chapter: Azoles, Their Importance, and Applications

Cited by 7 publications

References 50 publications

Synthesis and investigation of antibacterial activity of 1-(4-substituted phenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives

Synthesis and investigation of antibacterial activity of 1-(4-substituted phenyl)-5-oxopyrrolidine-3-carbohydrazide derivatives

Evolutionary diversity of the control of the azole response by Tra1 across yeast species

Evolutionary diversity of the control of the azole response by Tra1 across yeast species

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