首页|黄河三角洲盐碱土壤来源真菌Penicillium terrigenum RD 4-3次级代谢产物及其抗炎抗肿瘤活性

黄河三角洲盐碱土壤来源真菌Penicillium terrigenum RD 4-3次级代谢产物及其抗炎抗肿瘤活性

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目的 研究黄河三角洲盐碱土壤中真菌Penicillium terrigenum RD 4-3的次级代谢产物及其生物活性.方法 采用多种色谱分离技术对真菌液态发酵次级代谢产物进行分离纯化,并根据化合物的理化性质及波谱数据进行结构鉴定,同时进行细胞毒活性和NO检测,探究其抗肿瘤与抗炎活性.结果 最终从Penicillium terrigenum RD 4-3发酵产物中分离鉴定14个单体化合物,分别为倍半萜类14-hydroxypetasol(1)、6-dehydropetasol(2)、isopetasol(3)、acremeremophilane G(4)、phomenone(6)、7-hydroxypetasol(7)、sporogen-AO1(9)、petasol(10)、JBIR-28(11)、JBIR-27(12)、3-acetyl-13-deoxyphome(13)、penicilleremophilane A(14),以及苯的衍生物 3-chloro-4-hydroxypheylacetamide(5)、phenols(8),其中化合物 1(14-hydroxypetasol)为新化合物.活性结果显示,化合物 6(phomenone)和9(sporogen-AO1)对非小细胞肺癌细胞A549和H1299均具有显著的抗肿瘤活性,IC50值均在10 μmol/L以下.在浓度为 50 μmol/L 时,化合物 6(phomenone)、10(petasol)、11(JBIR-28)在 LPS 诱导的 炎症模型中表现出一定的抗炎活性.初步的构效关系研究发现,6,7位的氧环结构可以显著提高化合物的抗肿瘤及抗炎活性.结论 真菌Penicillium terrigenum RD 4-3的次级代谢产物中的倍半萜类在抗肿瘤抗炎先导化合物发现方面具有巨大研发潜力.
Secondary metabolites and their activities of Penicillium terrigenum RD 4-3 isolated from saline-alkali soil in the Yellow River Delta
Objective To study the secondary metabolites and biological activities of fungus Penicillium terrigenum RD 4-3 isolated from saline-alkali soil in the Yellow River Delta.Methods The secondary metabolites were isolated and purified using various chromatographic methods from culture broth,and the structures of the pure compounds were iden-tified based on their physicochemical properties and spectral data.Cytotoxic activity and NO detection were performed to explore antineoplastic activity and anti-inflammatory activity.Results Fourteen pure compounds were isolated and identified from the extracts of Penicillium terrigenum RD 4-3,including sesquiterpenes 14-hydroxypetasol(1),6-dehy-dropetasol(2),isopetasol(3),acremeremophilane G(4),phomenone(6),7-hydroxypetasol(7),sporogen-AO1(9),petasol(10),JBIR-28(11),JBIR-27(12),3-acetyl-13-deoxyphome(13)and penicilleremophilane A(14),and benzene derivatives 3-chloro-4-hydroxypheylacetamide(5)and phenols(8),among which 14-hydroxypetasol was a new compound.The activity results showed that phomenone(6)and sporogen-AO1(9)exhibited significant antitu-mor activities against non-small cell lung cancer cells A549 and H1299,with IC50 values below 10 μmol/L.At a con-centration of 50 μmol/L,phomenone,petasol and JBIR-28 exhibited anti-inflammatory activity in the LPS-induced in-flammation model.Preliminary structure-activity relationship revealed that the 6,7-epoxyl structure could significantly increase the antitumor and anti-inflammatory activities of the compounds.Conclusion The sesquiterpenes of the sec-ondary metabolitesfrom fungus Penicillium terrigenum RD 4-3 from the Yellow River Delta exhibit great potential in the discovery of antitumor and anti-inflammatory lead compounds.

Yellow River DeltaFungiPenicillium terrigenum RD 4-3Secondary metabolitesAntitumor activityAnti-inflammatory activity

张臻、苗双、齐世洲、武艳、蔡国伟、宫凯凯

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滨州医学院附属医院医学研究中心,山东滨州 256603

滨州医学院附属医院国家临床药物试验机构,山东滨州 256603

黄河三角洲 真菌 Penicillium terrigenum RD 4-3 次级代谢产物 抗肿瘤活性 抗炎活性

国家自然科学基金

81903537

2024

山东大学学报(医学版)
山东大学

山东大学学报(医学版)

CSTPCD北大核心
影响因子:0.841
ISSN:1671-7554
年,卷(期):2024.62(3)
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