Structure–activity relationship and biofilm formation-related gene targets of oleanolic acid-type saponins from Pulsatilla chinensis against Candida albicans

[Display omitted] •The SAR of antifungal oleanolic acid-type saponins from P. chinensis were revealed.•23-Hydroxyl group and free carboxyl at C-28 were essential for antifungal activity.•A disaccharide or trisaccharide moiety at C-3 was favorable for antifungal activity.•Typical saponin PB3 downregu...

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Veröffentlicht in:Bioorganic chemistry 2024-05, Vol.146, p.107311-107311, Article 107311
Hauptverfasser: Tan, Junfeng, Zhang, Zengguang, Zheng, Dan, Mu, Yu, Cao, Bixuan, Yang, Junwei, Han, Li, Huang, Xueshi
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Sprache:eng
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Zusammenfassung:[Display omitted] •The SAR of antifungal oleanolic acid-type saponins from P. chinensis were revealed.•23-Hydroxyl group and free carboxyl at C-28 were essential for antifungal activity.•A disaccharide or trisaccharide moiety at C-3 was favorable for antifungal activity.•Typical saponin PB3 downregulated Bcr1-dependent adhesins pathway in C. albicans.•PB3 induced the endogenous ROS-mediated oxidative damage leading to cell death. In the course of our investigations of antifungal natural products, the structure–activity relationship and antifungal activities of oleanolic acid-type saponins (1–28) from Pulsatilla chinensis against human and plant pathogenic fungi were elucidated. The analysis of structure–activity relationship of oleanolic acid-type saponins showed that the free carboxyl at C-28 was essential for their antifungal activities; the free hydroxyl group at the C-23 site of oleanolic acid-type saponins played a crucial role in their antifungal activities; the oligosaccharide chain at C-3 oleanolic acid-type saponins showed significant effects on antifungal efficacy and a disaccharide or trisaccharide moiety at position C-3 displayed optimal antifungal activity. The typical saponin pulchinenoside B3 (16, PB3) displayed satisfactory antifungal activity against human and plant pathogenic fungi, especially, C. albicans with an MIC value of 12.5 μg/mL. Furthermore, PB3 could inhibit the biofilm formation of C. albicans through downregulating the expression of the integrated network of biofilm formation-associated transcription factors (Bcr1 Efg1, Ndt80, Brg1, Rob1 and Tec1) and adhesion-related target genes (HWP1, ALS1, and ALS3). Meanwhile, we found that PB3 could effectively destroy the mature biofilm of C. albicans by the oxidative damage and inducing mitochondria-mediated apoptosis in cells.
ISSN:0045-2068
1090-2120
DOI:10.1016/j.bioorg.2024.107311