2025年04月05日 星期六

广西师范大学学报(自然科学版) ›› 2025, Vol. 43 ›› Issue (2): 247-257.doi: 10.16088/j.issn.1001-6600.2024082203

• 药用资源研究 • 上一篇    下一篇

嗜盐真菌Cladosporium cladosporioides GXIMD 00533次级代谢产物及其生物活性研究

傅春青1,2, 梁春祥1,2, 梁莉芬1,2, 高程海1,2, 刘永宏1,2, 徐新亚1,2*   

  1. 1.广西中医药大学 海洋药物研究院, 广西 南宁 530200;
    2.广西海洋药物重点实验室(广西中医药大学), 广西 南宁 530200
  • 收稿日期:2024-08-22 出版日期:2025-03-05 发布日期:2025-04-02
  • 通讯作者: 徐新亚(1981—), 男, 河南项城人, 广西中医药大学研究员, 博士。E-mail: xuxy@gxtcmu.edu.cn
  • 基金资助:
    国家自然科学基金(42066006); 广西自然科学基金(2024GXNSFAA010403,2021GXNSFDA075010); 广西中医药大学桂派杏林拔尖人才资助项目(2022C011); 广西中医药大学“岐黄工程”团队培育项目(202407); 中药学广西一流学科(桂教科研〔2022〕1号)

Secondary Metabolites and Biological Activities of Halophilic Fungus Cladosporium cladosporioides GXIMD 00533

FU Chunqing1,2, LIANG Chunxiang1,2, LIANG Lifen1,2, GAO Chenghai1,2, LIU Yonghong1,2, XU Xinya1,2*   

  1. 1. Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning Guangxi 530200, China;
    2. Guangxi Key Laboratory of Marine Drugs (Guangxi University of Chinese Medicine), Nanning Guangxi 530200, China
  • Received:2024-08-22 Online:2025-03-05 Published:2025-04-02

摘要: 本文采用高盐度真菌培养基,对广西北海竹林盐场来源枝孢属嗜盐真菌Cladosporium cladosporioides GXIMD 00533的次级代谢产物进行研究。采用硅胶、反相ODS柱色谱和半制备HPLC等分离手段对该菌株发酵产物进行分离纯化,得到16个单体化合物,根据核磁共振波谱数据对分离得到的化合物进行结构鉴定,鉴定为4个内酯类化合物iso-cladospolide B(1)、cladospolide B(2)、pandangolide 1(3)和thiocladospolide F(4),2个甾醇类化合物cladosporisteroid B(5)和(22E,24R)-3β,5α, 9α-三羟基-7,22-麦角甾二烯-6-酮(6),7个二酮哌嗪brevianamide F(7)、N-乙酰-L-苯丙氨酸(8)、环(L-脯氨酸-L-亮氨酸)(9)、环(L-丙氨酸-L-亮氨酸)(10)、环(L-缬氨酸-L-丙氨酸)(11)、环(L-甘氨酸-L-异亮氨酸)(12)和环(L-亮氨酸-L-甘氨酸)(13),1个氨基酸L-色氨酸(14),2个脂肪酸cladosporacid B(15)和(4R,5S,11R,2E)-4,5,11-三羟基-2-十二烯酸甲酯(16)。对所有化合物进行抗氧化、抗菌、α-葡萄糖苷酶抑制活性、细胞毒活性、抗藤壶附着活性和乙酰胆碱酯酶抑制活性评价。结果显示,化合物6和14具有显著的铁离子还原和抗氧化能力,强于阳性对照抗坏血酸(vitamin C, Vc);化合物6对α-葡萄糖苷酶具有一定程度的抑制活性,IC50为2.662 μmol/L;化合物4具有显著的抗藤壶附着活性,抗附着率为100%;部分化合物表现出一定的乙酰胆碱酯酶活性,其中化合物5抑制率达到54.98%。

关键词: 海水盐场, 嗜盐真菌, 枝孢属, 次级代谢产物, 海洋真菌

Abstract: The secondary metabolites of Cladosporium cladosporioides GXIMD 00533 from Guangxi Beihai Zhulin Salt Field, were studied by using high salinity medium. The fungal extract was separated and purified by silica gel, reversed phase ODS column chromatography and semi-preparative high performance liquid chromatography (HPLC) to obtain 16 compounds. Their structures were elucidated by NMR spectral data and identified as four lactone compounds: iso-cladospolide B (1), cladospolide B (2), pandangolide 1 (3), thiocladospolide F (4), two sterol compounds: cladosporisteroid B (5) and (22E,24R)-3β,5α,9α-trihydroxyergosta-7,22-dien-6-one (6), seven diketopiperazine: brevianamide F (7), N-acetyl-L-phenylalanine (8), cyclo (L-Pro-L-Leu) (9), cyclo (L-Ala-L-Leu) (10), cyclo (L-Val-L-Ala) (11), cyclo (L-Gly-L-Ile) (12), cyclo (L-Leu-L-Gly) (13), one amino acid: L-tryptophan (14), and two fatty acids: cladosporacid B (15) and (4R,5S,11R,2E)-4,5,11-trihydroxy-2-dodecenoate (16). The antioxidant, antibacterial, α-Glucosidase inhibitory, cytotoxic activities, anti-barnala adhesion and acetylcholinesterase inhibitory activities of all compounds were evaluated. Compounds 6 and 14 had significant iron ion reduction and antioxidant capacity. Compound 6 exhibited inhibitory activities on α-glucosidase with IC50 of 2.662 μmol·L-1; Compound 4 had significant anti-barnacle adhesion activity, and the anti-adhesion rate was 100%. Some of the compounds showed certain acetylcholinesterase activity, and the inhibitory rate of compound 5 reached 54.98%.

Key words: marine salt field, halophilic fungus, Cladosporium, secondary metabolite, marine fungus

中图分类号:  Q936; TQ28; P745

[1] HUANG Z H, NONG X H, LIANG X, et al. New tetramic acid derivatives from the deep-sea-derived fungus Cladosporium sp. SCSIO z0025[J]. Tetrahedron, 2018, 74(21): 2620-2626. DOI: 10.1016/j.tet.2018.04.010.
[2] 董锦润,李靖,陈玉惠,等.枝孢属真菌次生代谢产物中化学成分及其生物活性的研究进展[J].中草药,2021,52(19):6076-6087.DOI: 10.7501/j.issn.0253-2670.2021.19.031.
[3] SALVATORE M M, ANDOLFI A, NICOLETTI R. The genus Cladosporium: a rich source of diverse and bioactive natural compounds[J]. Molecules, 2021, 26(13): 3959. DOI: 10.3390/molecules26133959.
[4] WANG L P, HAN X L, ZHU G L, et al. Polyketides from the endophytic fungus Cladosporium sp. isolated from the mangrove plant Excoecaria agallocha[J]. Frontiers in Chemistry, 2018, 6: 344. DOI: 10.3389/fchem.2018.00344.
[5] CAO F, YANG Q, SHAO C L, et al. Bioactive 7-oxabicyclic[6.3.0] lactam and 12-membered macrolides from a gorgonian-derived Cladosporium sp. fungus[J]. Marine Drugs, 2015, 13(7): 4171-4178. DOI: 10.3390/md13074171.
[6] ZHANG F Z, LI X M, MENG L H, et al. Cladocladosin A, an unusual macrolide with bicyclo 5/9 ring system, and two thiomacrolides from the marine mangrove-derived endophytic fungus, Cladosporium cladosporioides MA-299[J]. Bioorganic Chemistry, 2020, 101: 103950. DOI: 10.1016/j.bioorg.2020.103950.
[7] MÉJANELLE L, LÒPEZ J F, GUNDE-CIMERMAN N, et al. Ergosterol biosynthesis in novel melanized fungi from hypersaline environments[J]. Journal of Lipid Research, 2001, 42(3): 352-358. DOI: 10.1016/S0022-2275(20)31658-8.
[8] 陈显强,邢楠楠,黄亮华,等.嗜盐真菌多样性及其抗肿瘤活性研究[J].广西科学,2020,27(5):526-531.DOI: 10.13656/j.cnki.gxkx.20201231.01.
[9] 李海艳,陆春菊,张耿思,等.北海竹林盐场极端嗜盐真菌的多样性及其抑菌活性研究[J].广西科学,2023,30(3): 478-484.DOI: 10.13656/j.cnki.gxkx.20230710.006.
[10] 袁凤娟,于璐,张萌,等.面包树树叶类黄酮提取工艺优化及抗氧化性评价[J].广西科学,2022,29(6):1141-1150.DOI: 10.13656/j.cnki.gxkx.20230110.014.
[11] BENZIE I F, STRAIN J J. Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration[J]. Methods in Enzymology, 1999, 299: 15-27. DOI: 10.1016/s0076-6879(99)99005-5.
[12] ZHENG Y, ZHANG R F, HUANG F, et al. α-Glucosidase inhibitors derived from black soybean and their inhibitory mechanisms[J]. LWT, 2023, 189: 115502. DOI: 10.1016/J.LWT.2023.115502.
[13] ZHANG J, TANG X L, HAN X, et al. Sarcoglaucins A-I, new antifouling cembrane-type diterpenes from the South China Sea soft coral Sarcophyton glaucum[J]. Organic Chemistry Frontiers, 2019, 6(12): 2004-2013. DOI: 10.1039/C9QO00386J.
[14] DAI Y, LI K L, SHE J L, et al. Lipopeptide epimers and a phthalide glycerol ether with AChE inhibitory activities from the marine-derived fungus Cochliobolus lunatus SCSIO41401[J]. Marine Drugs, 2020, 18(11): 547. DOI: 10.3390/md18110547.
[15] 刘茜,张业.南方红豆杉提取物的抗氧化、抗肿瘤活性研究[J].广西师范大学学报(自然科学版),2016,34(4): 55-59.DOI: 10.16088/j.issn.1001-6600.2016.04.009.
[16] JIANG Q J, WEI N, HUO Y S, et al. Secondary metabolites of the endophytic fungus Cladosporium sp. CYC38[J]. Chemistry of Natural Compounds, 2020, 56(6): 1166-1169. DOI: 10.1007/s10600-020-03257-y.
[17] FUJII Y, FUKUDA A, HAMASAKI T, et al. Twelve-membered lactones produced by Cladosporium tenuissimum and the plant growth retardant activity of cladospolide B[J]. Phytochemistry, 1995, 40(5): 1443-1446. DOI: 10.1016/0031-9422(95)00414-3.
[18] GESNER S, COHEN N, ILAN M, et al. Pandangolide 1a, a metabolite of the sponge-associated fungus Cladosporium sp., and the absolute stereochemistry of pandangolide 1 and iso-cladospolide B[J]. Journal of Natural Products, 2005, 68(9): 1350-1353. DOI: 10.1021/np0501583.
[19] WANG W X, FENG H M, SUN C X, et al. Thiocladospolides F-J, antibacterial sulfur containing 12-membered macrolides from the mangrove endophytic fungus Cladosporium oxysporum HDN13-314[J]. Phytochemistry, 2020, 178: 112462. DOI: 10.1016/j.phytochem.2020.112462.
[20] PANG X Y, LIN X P, WANG J F, et al. Three new highly oxygenated sterols and one new dihydroisocoumarin from the marine sponge-derived fungus Cladosporium sp. SCSIO41007[J]. Steroids, 2018, 129: 41-46. DOI: 10.1016/j.steroids.2017.12.001.
[21] 韩秀丽,林贞健,陶洪文,等.红海榄共生真菌Penicillium sp.HK13-8细胞毒活性成分研究[J].中国海洋药物,2009,28(5):11-16.DOI: 10.13400/j.cnki.cjmd.2009.05.004.
[22] KOBAYASHI M, AOKI S, GATO K, et al. Marine natural products. XXXIV. Trisindoline, a new antibiotic indole trimer, produced by a bacterium of Vibrio sp. separated from the marine sponge Hyrtios altum[J]. Chemical & Pharmaceutical Bulletin, 1994, 42(12): 2449-2451. DOI: 10.1248/cpb.42.2449.
[23] 王慧娜,尹志峰,尹鑫,等.金丝草化学成分及其体外抗HBV活性[J].中成药,2019,41(6):1308-1312.DOI: 10.3969/j.issn.1001-1528.2019.06.022.
[24] ZHAO P J, WANG H X, LI G H, et al. Secondary metabolites from endophytic Streptomyces sp. Lz531[J]. Chemistry & Biodiversity, 2007, 4(5): 899-904. DOI: 10.1002/cbdv.200790078.
[25] DING Z G, ZHAO J Y, YANG P W, et al. 1H and 13C NMR assignments of eight nitrogen containing compounds from Nocardia alba sp. nov (YIM 30243T)[J]. Magnetic Resonance in Chemistry, 2009, 47(4): 366-370. DOI: 10.1002/mrc.2393.
[26] COURSINDEL T, RESTOUIN A, DEWYNTER G, et al. Stereoselective ring contraction of 2,5-diketopiperazines: an innovative approach to the synthesis of promising bioactive 5-membered scaffolds[J]. Bioorganic Chemistry, 2010, 38(5): 210-217. DOI: 10.1016/j.bioorg.2010.05.002.
[27] HARIZANI M, KATSINI E, GEORGANTEA P, et al. New chlorinated 2,5-diketopiperazines from marine-derived bacteria isolated from sediments of the Eastern Mediterranean Sea[J]. Molecules, 2020, 25(7): 1509. DOI: 10.3390/molecules25071509.
[28] ZHANG S X, MA Y G, MA R H, et al. Combination of medium- and high-pressure liquid chromatography for isolation of L-tryptophan (Q-marker) from Medicago sativa extract[J]. Separations, 2022, 9(9): 240. DOI: 10.3390/separations 9090240.
[29] PENG X P, WANG Y, ZHU G L, et al. Fatty acid derivatives from the halotolerant fungus Cladosporium cladosporioides[J]. Magnetic Resonance in Chemistry, 2018, 56(1): 18-24. DOI: 10.1002/mrc.4659.
[30] HIROTA H, HIROTA A, SAKAI H, et al. Absolute stereostructure determination of cladospolide A using MTPA ester method[J]. Bulletin of the Chemical Society of Japan, 1985, 58(7): 2147-2148. DOI: 10.1246/bcsj.58.2147.
[31] GOKUL RAJ K, MANIKANDAN R, ARULVASU C, et al. Anti-proliferative effect of fungal taxol extracted from Cladosporium oxysporum against human pathogenic bacteria and human colon cancer cell line HCT 15[J]. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2015, 138: 667-674. DOI: 10.1016/j.saa.2014.11.036.
[32] WATANABE S, TOGASHI S, TAKAHASHI N, et al. L-tryptophan as an antioxidant in human placenta extract[J]. Journal of Nutritional Science and Vitaminology, 2002, 48(1): 36-39. DOI: 10.3177/jnsv.48.36.
[33] 刘岩,李翔宇,李成会.色氨酸营养研究进展[J].中国饲料,2019(5):50-53.DOI: 10.15906/j.cnki.cn11-2975/s.20190512.
[34] 王斌.L-色氨酸缓解动物肠道炎症的作用机制研究[D].北京:中国农业大学,2018.
[35] 翁辉廉,陆泳.L-色氨酸的生理性安眠作用[J].中国医院药学杂志,1988,8(3):21-22.
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