Journal of Shandong University (Health Sciences) ›› 2024, Vol. 62 ›› Issue (3): 28-38.doi: 10.6040/j.issn.1671-7554.0.2023.1125

• Preclinical Medicine • Previous Articles     Next Articles

Secondary metabolites and their activities of Penicillium terrigenum RD 4-3 isolated from saline-alkali soil in the Yellow River Delta

ZHANG Zhen1, MIAO Shuang1, QI Shizhou1, WU Yan1, CAI Guowei2, GONG Kaikai1   

  1. 1. Medical Research Center, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China;
    2. CFDA Certified Clinical Trials Institution, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China
  • Published:2024-05-06

PDF (PC)

63

Abstract: 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 identified 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-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)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 antitumor activities against non-small cell lung cancer cells A549 and H1299, with IC50 values below 10 μmol/L. At a concentration of 50 μmol/L, phomenone, petasol and JBIR-28 exhibited anti-inflammatory activity in the LPS-induced inflammation 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 secondary 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.

Key words: Yellow River Delta, Fungi, Penicillium terrigenum RD 4-3, Secondary metabolites, Antitumor activity, Anti-inflammatory activity

CLC Number: 

  • R574
[1] Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B influenzæ[J]. Br J Exp Pathol, 1929, 10(3): 226-236.
[2] Schueffler A, Anke T. Fungal natural products in research and development[J]. Nat Prod Rep, 2014, 31(10): 1425-1448.
[3] 刘玉斌,韩美,刘延荣,等.黄河三角洲土壤盐分养分空间分异规律研究[J].人民黄河, 2018, 40(2): 76-80. LIU Yubin, HAN Mei, LIU Yanrong, et al. Spatial distribution of soil salinity and nutrients in the Yellow River Delta[J]. Yellow River, 2018, 40(2): 76-80.
[4] 谭小丽,王岩宏,韩卫东.黄河三角洲湿地土壤剖面理化特征分析[J].资源节约与环保, 2018, 5(12): 9247-9250. TAN Xiaoli, WANG Yanhong, HAN Weidong. Analysis of physical and chemical characteristics of wetland soil profile in Yellow River Delta[J]. Resources Economization & Environment Protection, 2018, 5(12): 9247-9250.
[5] 许言超,刘培培,王乂,等. 黄河三角洲植物真菌的分离、活性菌株筛选及活性产物鉴定[J]. 中国海洋药物, 2014, 33(4): 15-20. XU Yanchao, LIU Peipei, WANG Yi, et al. Isolation of plant fungi, screening of active strains and identification of active products in the Yellow River Delta[J]. Chinese Journal of Maeine Medicine, 2014, 33(4): 15-20.
[6] 陈正乾,刘培培,王乂,等.黄河三角洲土曲霉Aspergillus terreus OUCMDZ-1925中具抗菌活性的聚酮类天然产物[J].菌物学报, 2013, 32(2): 277-285. CHEN Zhengqian, LIU Peipei, WANG Yi, et al. Polyketide natural products with antimicrobial activity in Aspergillus terreus OUCMDZ-1925 in the Yellow River Delta[J]. Mycosystema, 2013, 32(2): 277-285.
[7] 曲鹏,刘培培,付鹏,等.黄河三角洲耐盐真菌Penicillium chrysogenum HK14-01的次生代谢产物[J].微生物学报, 2012, 52(9): 1103-1112. QU peng, LIU Peipei, FU Peng, et al. Secondary metabolites of salt-tolerant fungus Penicillium chrysogenum HK14-01 in the Yellow River Delta[J]. Acta Microbiologica Sinica, 2012, 52(9): 1103-1112.
[8] 王聪,刘培培,王乂,等. 海洋来源放线菌Streptomyces parvulus OUCMDZ-2554产放线菌素D的发酵条件优化[J]. 中国海洋药物, 2014, 33(3): 34-42. WANG Cong, LIU Peipei, WANG Yi, et al. Optimization of fermentation conditions for actinomycin D production by Streptomyces parvulus OUCMDZ-2554 from marine actinomyces[J]. Chinese Journal of Marine Medicine, 2014, 33(3): 34-42.
[9] Fu P, Liu P, Qu H, et al. Alpha-pyrones and diketopiperazine derivatives from the marine-derived actinomycete Nocardiopsis dassonvillei HR10-5[J]. J Nat Prod, 2011,74(10):2219-2223.
[10] Xu Y, Wang C, Liu H, et al. Meroterpenoids and isocoumarinoids from a Myrothecium fungus associated with Apocynum venetum[J]. Mar Drugs, 2018, 10(1): 1-13.
[11] Wang C, Li J, Yang R, et al. Petasins from the rhizomes of Ligularia fischeri and its derivatives[J]. Records of Natural Products, 2014, 8(2): 156-164.
[12] Li S, Qin C, Cui S, et al. Discovery of a natural-product-derived preclinical candidate for once-weekly treatment of type 2 diabetes[J]. J Med Chem, 2019, 62(5): 2348-2361.
[13] Sugama K, Hayashi K, Nakagawa T, et al. Sesquiterpenoids from Petasites fragrans[J]. Phytochemistry, 1983, 22(7): 1619-1622.
[14] Sugawara F, Hallock YF, Bunkers GD, et al. Phytoactive eremophilanes produced by the weed pathogen Drechslera gigantea[J]. Biosci Biotech Bioch, 1993, 57(2): 236-239.
[15] Cheng ZB, Zhao JJ, Liu D, et al. Eremophilane-type sesquiterpenoids from an Acremonium sp. Fungus isolated from deep-sea sediments[J]. J Nat Prod, 2016, 79(4): 1035-1047.
[16] Davis RA, Watters D, Healy PC. The isolation and synthesis of 3-chloro-4-hydroxyphenylacetamide produced by a plant-associated microfungus of the genus Xylaria[J]. Tetrahedron Lett, 2005, 46(6): 919-921.
[17] Motohashi K, Hashimoto J, Inaba S, et al. New sesquiterpenes, JBIR-27 and -28, isolated from a tunicate-derived fungus, Penicillium sp. SS080624SCf1[J]. J Antibiot, 2009, 62(5): 247-250.
[18] Davis RA, Innocenti A, Poulsen SA, et al. Carbonic anhydrase inhibitors. Identification of selective inhibitors of the human mitochondrial isozymes VA and VB over the cytosolic isozymes I and II from a natural product-based phenolic library[J]. Bioorgan Med Chem, 2010, 18(1): 14-18.
[19] 高忠杰,曲莉,孙振青,等.烟草内生真菌土曲霉中一个新的苯乙酸类化合物[J].中国药物化学杂志, 2021, 31(8): 597-604. GAO Zhongjie, QU Li, SUN Zhenqing, et al. A new hydroxyphenylacetic acid derivative isolated from the endophyte Aspergillus terreus of Nicotiana tabacum L[J]. Chinese Journal of Medicinal Chemistry, 2021, 31(8): 597-604.
[20] 蔡由生,刘海利,龚景旭,等.中国湛江木榄(Bruguiera gymnorrhiza)的化学成分研究[J]. 中国海洋药物, 2011, 30(1): 15-18. CAI Yousheng, LIU Haili, GONG Jingxu, et al. Chemical constituents of mangrove plant Bruguiera gymnorrhiza[J]. Chinese Journal of Marine Drugs, 2011, 30(1): 15-18.
[21] Huang YF, Qiao L, Lv AL, et al. Eremophilane sesquiterenes from the marine fungus Penicillium sp. BL27-2[J]. Chinese Chem Lett, 2008, 19(5): 562-564.
[22] Daengrot C, Rukachaisirikul V, Tansakul C, et al. Eremophilane sesquiterpenes and diphenyl thioethers from the soil fungus Penicillium copticola PSU-RSPG138[J]. J Nat Prod, 2015, 78(4): 615-622.
[23] 刘德胜.黄河三角洲盐碱地真菌多样性及活性次级代谢产物的初步研究[D]. 青岛:中国海洋大学, 2014.
[24] Fraga BM. Natural sesquiterpenoids[J]. Nat Prod Rep, 2013, 30(9): 1226-1264.
[25] Dickschat JS. Bacterial terpene cyclases[J]. Nat Prod Rep, 2016, 33(1): 87-110.
[26] Mai F, Glomb MA. Structural and sensory characterization of novel sesquiterpene lactones from Iceberg lettuce[J]. J Agric Food Chem, 2016, 64(1): 295-301.
[27] Raupp FM, Spring O. New sesquiterpene lactones from Sunflower root exudate as germination stimulants for Orobanche cumana[J]. J Agric Food Chem, 2013, 61(44): 10481-10487.
[28] Chen R, Feng T, Li M, et al. Characterization of tremulane sesquiterpene synthase from the basidiomycete Irpex lacteus[J]. Org Lett, 2022, 24(31): 5669-5673.
[29] Cheong CB, Peh G, Wei Y, et al. A spirobicyclo[3.1.0] terpene from the investigation of sesquiterpene synthases from Lactarius deliciosus[J]. ACS Chem Bio, 2023, 18(1): 134-140.
[30] Scavo A, Rial C, Varela RM, et al. Influence of genotype and harvest time on the Cynara cardunculus L. sesquiterpene lactone profile[J]. J Agric Food Chem, 2019, 67(23): 6487-6496.
[31] Abraham W. Bioactive sesquiterpenes produced by fungi are they useful for humans as well[J]. Curr Med Chem, 2001, 8(6): 583-606.
[32] Dambolena JS, Zunino MP, Herrera JM, et al. Terpenes: natural products for controlling insects of importance to human health-a structure-activity relationship study[J]. Psyche-J Entomol, 2016: 1-17. doi:10.1155/2016/4595823.
[33] Quintana J, Estevez F. Recent advances on cytotoxic sesquiterpene lactones[J]. Curr Pharm Design, 2018, 24(36): 4355-4361.
[1] ZHANG Pengliang, ZHANG Longteng, LI Ailing, SHEN Tao, LOU Hongxiang, WANG Xiaoning. Isolation of Leptosphaerins H and I, two new xanthones from the endophytic fungus Leptosphaeria sp. and their anti-inflammatory activity [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(11): 27-31.
[2] XU Wenjing, HAN Xiaomin, ZHANG Jing, PAN Zhuo, LI Fengqin, ZHANG Lishi. Survey on fungi contamination of wheat harvested in 2015 from Anhui Province of China [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(9): 92-96.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] LI Ning, LI Juan, XIE Yan, LI Peilong, WANG Yunshan, DU Lutao, WANG Chuanxin. Expression of LncRNA AL109955.1 in 80 cases of colorectal cancer and its effect on cell proliferation, migration and invasion[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 38 -46 .
[2] LUO Xin, HE Bing, NIE Qingsheng, HOU Zhenbo, DONG Jun, LI Yuhua, ZENG Xiangqin, LIU Wei, KONG Demin, CAO Jinfeng. Comparison of the value of mono-exponential mode and diffusion kurtosis imaging mode in grading clear cell renal cell carcinoma using magnetic resonance diffusion-weighted imaging[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 89 -95 .
[3] Di ZHANG,Meng YU,Xia LIU. A general overview of neuromodulation[J]. Journal of Shandong University (Health Sciences), 2020, 1(8): 50 -60 .
[4] SUN Yifeng, GAO Yu, LIANG Yongyuan, GAO Yang. Expression of CPLX2 and its in vitro effects on the proliferation migration and invasion of hepatocellular carcinoma cells[J]. Journal of Shandong University (Health Sciences), 2020, 1(9): 34 -39 .
[5] . [J]. Journal of Shandong University (Health Sciences), 2020, 1(9): 103 -105 .
[6] . [J]. Journal of Shandong University (Health Sciences), 2020, 1(9): 116 -118 .
[7] ZHU Yuhua,ZHANG Chunqing,REN Wanhua,MA Yanli,ZHAO Youan. Cloning and screening of the recombinant plasmids[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(4): 351 -356 .
[8] SUN Wei-peng,ZOU Wei-wei,XI Yan-wei,ZHANG Na. Oral absorption effect of liposomes with different sizes on TFu[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(6): 639 -642 .
[9] TANGShu-mei,PANＸiao-jun. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(5): 475 -477 .
[10] GUOMin,LIYAn-qing,LIUChuan-yong,XIEDong-ping,GUOYU-ting,ZUOXiu-li,ZENGJuan. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(5): 514 -518 .
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd