黄河三角洲盐碱地来源真菌Penicillium camembertiRD-37次级代谢产物的分离鉴定及活性评估

doi:10.6040/j.issn.1671-7554.0.2025.0931

摘要/Abstract

摘要： 目的研究黄河三角洲盐碱地来源的真菌Penicillium camemberti RD-37的次级代谢产物及其生物活性。方法综合运用化学萃取、薄层色谱(thin layer chromatography, TLC)、ODS柱色谱(octadecylsilyl, ODS)和半制备型高效液相色谱(high performance liquid chromatography, HPLC)等分离技术对该株真菌发酵产物进行分离纯化;通过核磁共振(nuclear magnetic resonance, NMR)、质谱等波谱技术并结合文献数据比对,确定化合物结构。采用CCK-8法和Griess法初步评估单体化合物的抗肿瘤活性和抗炎活性。结果从真菌Penicillium camemberti RD-37大米发酵产物的乙酸乙酯提取物中共分离鉴定出11个单体化合物,分别为6-(methyl 3-methylbutanoate)-7-hydroxy-5-methoxy-4-methylphthalan-1-one(1)、7-hydroxy-5-methoxy-4-methyl-6-(3-methyl-4-oxopentyl)-phthalan-l-one(2)、F01-1358B(3)、Methyl mycophenolic acid(4)、6-((2E, 6E)-3, 7-dimethyldeca-2, 6-dienyl)-7-hydroxy-5-methoxy-4-methylphtanlan-1-one(5)、5,7-dihydroxy-4-methylisobenzofuran-1(3H)-one(6)、(2-hydroxypropan-2-yl)-6-methyl-2, 3-dihydrobenzofuran-4-ol(7)、Radstrictin K(8)、2, 3-dihydro-2-hydroxy-2, 4-dimethyl-5-trans-propenylfuran-3-one(9)、苯甲酸(10)、对甲氧基苯甲酸(11)。活性检测结果表明,化合物4(methyl mycophenolic acid)对人结肠腺癌细胞RKO和人卵巢癌细胞A2780细胞均表现出明显的细胞毒活性,IC₅₀值分别为7.7 μmol/L和8.2 μmol/L。在浓度为30 μmol/L时,脂多糖(lipopolysaccharide, LPS)诱导的炎症模型中化合物1、6、8、9、10和11对小鼠单核巨噬细胞RAW264.7表现出一定的抗炎活性,NO抑制率分别为45.9%、54.0%、62.3%、96.0%、59.5%和55.8%。结论真菌Penicillium camemberti RD-37具有产抗肿瘤抗炎活性成分的潜力,化合物4对肿瘤细胞具有显著的抑制活性。

关键词: 黄河三角洲, 真菌, Penicillium camemberti RD-37, 次级代谢产物, 细胞毒活性, 抗炎活性

Abstract: Objective To analyze the secondary metabolites and biological activities of the fungus Penicillium camemberti RD-37, which was isolated from the saline-alkaline soil of the Yellow River Delta. Methods The fermentation extract of this particular fungal strain was isolated and purified through integrated application of separation techniques, including chemical extraction, thin layer chromatography(TLC), octadecylsilyl column chromatography(ODS), and semi-preparative high performance liquid chromatography(HPLC). The structures of the compounds were determined using spectroscopic techniques such as nuclear magnetic resonance(NMR)and mass spectrometry, combined with a comparison of the literature data. The anti-tumor and anti-inflammatory activities of pure compounds were evaluated using CCK-8 and Griess assays. Results Eleven compounds were isolated and identified from the ethyl acetate extract of the rice fermentation of the fungus Penicillium camemberti RD-37, including 6-(methyl 3-methylbutanoate)-7-hydroxy-5-methoxy-4-methylphthalan-1-one(1), 7-hydroxy-5-methoxy-4-methyl-6-(3-methyl-4-oxopentyl)-phthalan-l-one(2), F01-1358B(3), Methyl mycophenolic acid(4), 6-((2E, 6E)-3,7-dimethyldeca-2, 6-dienyl)-7-hydroxy-5-methoxy-4-methylphtanlan-1-one(5), 5,7-dihydroxy-4-methylisobenzofuran-1(3H)-one(6),(2-hydroxypropan-2-yl)-6-methyl-2,3-dihydrobenzofuran-4-ol(7), Radstrictin K(8), 2,3-dihydro-2-hydroxy-2, 4-dimethyl-5-trans-propenylfuran-3-one(9), Benzoic acid(10), p-methoxybenzoic acid(11). The activity results indicated that compound 4(Methyl mycophenolic acid)exhibited significant cytotoxic activities against both human colorectal adenocarcinoma cells RKO and human ovarian cancer cells A2780 cells, with IC₅₀ values of 7.7 μmol/L and 8.2 μmol/L, respectively.In the LPS-induced inflammation model, at a concentration of 30 μmol/L, compounds 1, 6, 8, 9, 10 and 11 exhibited anti-inflammatory activities in mouse mononuclear macrophages cells RAW264.7, with NO inhibition rates of 45.9%, 54.0%, 62.3%, 96.0%, 59.5%, and 55.8%, respectively. Conclusion The fungus Penicillium camemberti RD-37 has the potential to produce compounds with antitumor and anti-inflammatory activities. Compound 4 exhibits significant inhibitory activity against tumor cells.

Key words: Yellow River Delta, Fungi, Penicillium camemberti RD-37, Secondary metabolites, Cytotoxic activity, Anti-inflammatory activity

中图分类号:

吕文元,司婕,任思齐,张晓琦,方舟,苗双,宫凯凯. 黄河三角洲盐碱地来源真菌Penicillium camembertiRD-37次级代谢产物的分离鉴定及活性评估[J]. 山东大学学报 (医学版), 2026, 64(5): 10-18.

LYU Wenyuan, SI Jie, REN Siqi, ZHANG Xiaoqi, FANG Zhou, MIAO Shuang, GONG Kaikai. Isolation, identification, and activity evaluation of secondary metabolites from a fungus Penicillium camemberti RD-37 derived from saline-alkaline soil of the Yellow River Delta[J]. Journal of Shandong University (Health Sciences), 2026, 64(5): 10-18.

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