Structurally diverse triterpenoids with antibacterial activities from Euphorbia humifusa

• Published in: Bioorganic chemistry 2024-12, Vol.153, p.107915, Article 107915
• Main Authors: Xia, Ru-Feng, Wei, Yu-Ru, Zhang, Cheng-Qi, Huang, Yan, Chen, Ming-Sheng, Yuan, Xiao-Yu, Zha, Hong-Jing, Lai, Ke-Dao, Xia, Xian, Wan, Luo-Sheng
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antibacterial activity; Antibiofilm activity; Bacillus cereus - drug effects; Crystallography, X-Ray; Dose-Response Relationship, Drug; Euphorbia - chemistry; Euphorbia humifusa; Euphorbiaceae; Microbial Sensitivity Tests; Molecular Structure; Staphylococcus aureus - drug effects; Staphylococcus epidermidis - drug effects; Structure-Activity Relationship; Triterpenes - chemistry; Triterpenes - isolation & purification; Triterpenes - pharmacology; Triterpenoid
• ISSN: 0045-2068; 1090-2120; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107915

An exploration of antibacterial components from the whole plant of Euphorbia humifusa led to the isolation of 14 new triterpenoids, euphohumifusoids A–N (1–7 and 9–15), as well as four known analogues (8 and 16–18). Their structures were elucidated by extensively analysis of the spectroscopic data and X-ray crystallography using Cu Kα radiation. Among them, euphohumifusoid A (1) bears an unique 6(7→8)abeo scaffold originated from a D:C-friedo-oleanane skeleton for the first time, euphohumifusoids H and I (9 and 10) possess a rare α,β-unsaturated-γ-lactone chain originated from 25,26,27-trinordammaranes, and euphohumifusoid L (13) is a highly modified 3,4-seco-25,26,27-trinorcycloartane. Notably, in antibacterial bioassay, compound 1 displayed excellent antibacterial activities against Bacillus cereus, Staphylococcus aureus, and S.epidermidis with MIC of 12.5, 25, and 25 μg/mL, comparable to the positive controls, kanamycin and streptomycin. Upon exposure to 1 and 2 MIC of 1, B.cereus underwent drastic morphological changes, resulting in complete disruption of the cells. Meanwhile, compound 1 also exhibited remarkable antibiofilm activity against B.cereus at 1 MIC and 2 MIC. [Display omitted] •18 Structurally diverse triterpenoids including 14 novel ones were isolated from Euphorbia humifusa.•Compound 1 bears an unique 6(7→8)abeo scaffold originated from a D:C-friedo-oleanane skeleton for the first time.•Compounds 1 displays excellent antibacterial effect against B. cereus, comparable to the positive controls.•Compound 1 can disrupt the cellular structures and inhibit the biofilm formation of B. cereus. An exploration of antibacterial components from the whole plant of Euphorbia humifusa led to the isolation of 14 new triterpenoids, euphohumifusoids A–N (1–7 and 9–15), as well as four known analogues (8 and 16–18). Their structures were elucidated by extensively analysis of the spectroscopic data and X-ray crystallography using Cu Kα radiation. Among them, euphohumifusoid A (1) bears an unique 6(7 → 8)abeo scaffold originated from a D:C-friedo-oleanane skeleton for the first time, euphohumifusoids H and I (9 and 10) possess a rare α,β-unsaturated-γ-lactone chain originated from 25,26,27-trinordammaranes, and euphohumifusoid L (13) is a highly modified 3,4-seco-25,26,27-trinorcycloartane. Notably, in antibacterial bioassay, compound 1 displayed excellent antibacterial activities against Bacillus cereus, Staphylococcus aureus, and S.epidermidis with MIC of 12