Oteseconazole: a long-awaited diversification of the antifungal arsenal to manage recurrent vulvovaginal candidiasis (RVVC)

Vandecruys, Paul; Baldewijns, Silke; Sillen, Mart; Genechten, Wouter Van; Dijck, Patrick Van

doi:10.1080/14787210.2023.2233696

Cited by 10 publications

(3 citation statements)

References 72 publications

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“…Novel antifungal drugs that are active on Candida sp. are fosmanogepix (interferes with mannoprotein production in the cell wall by inhibiting Gwt1), ibrexafungerp and rezafungin (a triterpenoid and novel echinocandin that both inhibit the β-(1,3)-glucan biosynthesis) and oteseconazole (novel tetrazole inhibiting ergosterol biosynthesis and used to treat vaginal infections) [ 48 – 50 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic meta-analysis to identify potential antifungal targets in Candida albicans

Hefny,

Ji,

Elsemman

et al. 2024

BMC Microbiol

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Background Candida albicans is a fungal pathogen causing human infections. Here we investigated differential gene expression patterns and functional enrichment in C. albicans strains grown under different conditions. Methods A systematic GEO database search identified 239 “Candida albicans” datasets, of which 14 were selected after rigorous criteria application. Retrieval of raw sequencing data from the ENA database was accompanied by essential metadata extraction from dataset descriptions and original articles. Pre-processing via the tailored nf-core pipeline for C. albicans involved alignment, gene/transcript quantification, and diverse quality control measures. Quality assessment via PCA and DESeq2 identified significant genes (FDR < = 0.05, log2-fold change > = 1 or <= -1), while topGO conducted GO term enrichment analysis. Exclusions were made based on data quality and strain relevance, resulting in the selection of seven datasets from the SC5314 strain background for in-depth investigation. Results The meta-analysis of seven selected studies unveiled a substantial number of genes exhibiting significant up-regulation (24,689) and down-regulation (18,074). These differentially expressed genes were further categorized into 2,497 significantly up-regulated and 2,573 significantly down-regulated Gene Ontology (GO) IDs. GO term enrichment analysis clustered these terms into distinct groups, providing insights into the functional implications. Three target gene lists were compiled based on previous studies, focusing on central metabolism, ion homeostasis, and pathogenicity. Frequency analysis revealed genes with higher occurrence within the identified GO clusters, suggesting their potential as antifungal targets. Notably, the genes TPS2, TPS1, RIM21, PRA1, SAP4, and SAP6 exhibited higher frequencies within the clusters. Through frequency analysis within the GO clusters, several key genes emerged as potential targets for antifungal therapies. These include RSP5, GLC7, SOD2, SOD5, SOD1, SOD6, SOD4, SOD3, and RIM101 which exhibited higher occurrence within the identified clusters. Conclusion This comprehensive study significantly advances our understanding of the dynamic nature of gene expression in C. albicans. The identification of genes with enhanced potential as antifungal drug targets underpins their value for future interventions. The highlighted genes, including TPS2, TPS1, RIM21, PRA1, SAP4, SAP6, RSP5, GLC7, SOD2, SOD5, SOD1, SOD6, SOD4, SOD3, and RIM101, hold promise for the development of targeted antifungal therapies.

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Section: Introductionmentioning

confidence: 99%

Transcriptomic meta-analysis to identify potential antifungal targets in Candida albicans

Hefny,

Ji,

Elsemman

et al. 2024

BMC Microbiol

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“…Tetrazole is a privileged heterocycle existing in a range of biological and medicinally interesting compounds [1,2] with antifungal [3,4], antibacterial [5], anticancer [6,7], antiparasitic [8], and antihypertensive properties [9] including FDA approved drugs such as valsartan and cefmetazole [10,11] (Figure 1). The tetrazole ring can also be found in functional materials for photography, imaging, and military applications [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

Niu,

Wang,

Yan

et al. 2024

Beilstein J. Org. Chem.

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“…Tetrazole is a privileged heterocycle existing in a range of biological and medicinally interested compounds [1,2] with antifungal [3,4], antibacterial [5], anticancer [6,7], anti-parasitic [8],…”

Section: Introductionmentioning

confidence: 99%

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

Niu,

Wang,

Yan

et al. 2024

Preprint

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Oteseconazole: a long-awaited diversification of the antifungal arsenal to manage recurrent vulvovaginal candidiasis (RVVC)

Cited by 10 publications

References 72 publications

Transcriptomic meta-analysis to identify potential antifungal targets in Candida albicans

Transcriptomic meta-analysis to identify potential antifungal targets in Candida albicans

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

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