概要
北部湾藴育着丰富且亟待研究的海洋（微）生物资源,是活性天然产物的重要来源。本研究从涠洲岛珊瑚共附生构巢裸胞壳菌GXIMD 02509中分离获得一个多硫代二酮哌嗪生物碱和系列芳香聚酮类化合物,包含一个新化合物4a-O-methoxyarugosin H (1)。我们通过采用多种波、光谱学技术及对比文献方法鉴定了化合物的化学结构。化合物1∼5、7和10对786-O、SW1990和SW480等3株肿瘤细胞增殖具抑制活性,半抑制浓度（IC50）值为4.3∼33.4 µmol/L。化合物emestrin J (10)具有一个二硫桥键,还能够显著抑制786-O细胞克隆及迁移,诱导786-O细胞凋亡并阻滞细胞分裂在G2/M期,是一个潜在具抗肿瘤活性的先导化合物。
This is a preview of subscription content, log in via an institution to check access.
References
Alburae NA, Mohammed AE, Alorfi HS, et al., 2020. Nidulantes of Aspergillus (formerly Emericella): a treasure trove of chemical diversity and biological activities. Metabolites, 10(2):73. https://doi.org/10.3390/metabo10020073
Capon RJ, 2020. Extracting value: mechanistic insights into the formation of natural product artifacts-case studies in marine natural products. Nat Prod Rep, 37(1):55–79. https://doi.org/10.1039/C9NP00013E
Carroll AR, Copp BR, Davis RA, et al., 2022. Marine natural products. Nat Prod Rep, 39(6):1122–1171. https://doi.org/10.1039/D1NP00076D
Chen Y, Pang XY, He YC, et al., 2022. Secondary metabolites from coral-associated fungi: source, chemistry and bioactivities. J Fungi, 8(10):1043. https://doi.org/10.3390/jof8101043
Chi LP, Li XM, Wan YP, et al., 2020. Ophiobolin sesterterpenoids and farnesylated phthalide derivatives from the deep sea cold-seep-derived fungus Aspergillus insuetus SD-512. J Nat Prod, 83(12):3652–3660. https://doi.org/10.1021/acs.jnatprod.0c00860
Deshmukh SK, Gupta MK, Prakash V, et al., 2018. Mangrove-associated fungi: a novel source of potential anticancer compounds. J Fungi, 4(3):101. https://doi.org/10.3390/jof4030101
El-Kashef DH, Youssef FS, Reimche I, et al., 2021. Polyketides from the marine-derived fungus Aspergillus falconensis: in silico and in vitro cytotoxicity studies. Bioorg Med Chem, 29:115883. https://doi.org/10.1016/j.bmc.2020.115883
Guo L, Luo XW, Yang P, et al., 2021. Ilicicolin A exerts antitumor effect in castration-resistant prostate cancer via suppressing EZH2 signaling pathway. Front Pharmacol, 12: 723729. https://doi.org/10.3389/fphar.2021.723729
Huang BY, Peng S, Liu SF, et al., 2022. Isolation, screening, and active metabolites identification of anti-Vibrio fungal strains derived from the Beibu Gulf coral. Front Microbiol, 13:930981. https://doi.org/10.3389/fmicb.2022.930981
Kawahara N, Nozawa K, Nakajima S, et al., 1988. Studies on fungal products. Part 15. Isolation and structure determination of arugosin E from Aspergillus silvaticus and cycloisoemericellin from Emericella striata. J Chem Soc Perkin Trans, 1(4):907–911. https://doi.org/10.1039/P19880000907
Kralj A, Kehraus S, Krick A, et al., 2006. Arugosins G and H: prenylated polyketides from the marine-derived fungus Emericella nidulans var. acristata. J Nat Prod, 69(7): 995–1000. https://doi.org/10.1021/np050454f
Li Q, Chen CM, He Y, et al., 2019. Emeriones A–C: three highly methylated polyketides with bicyclo[4.2.0]octene and 3, 6-dioxabicyclo[3.1.0]hexane functionalities from Emericella nidulans. Org Lett, 21(13):5091–5095. https://doi.org/10.1021/acs.orglett.9b01680
Li Y, Yue Q, Krausert NM, et al., 2016. Emestrins: anticryptococcus epipolythiodioxopiperazines from Podospora australis. J Nat Prod, 79(9):2357–2363. https://doi.org/10.1021/acs.jnatprod.6b00498
Lu HM, Tan YH, Zhang YT, et al., 2022. Osteoclastogenesis inhibitory phenolic derivatives produced by the Beibu Gulf coral-associated fungus Acremonium sclerotigenum GXIMD 02501. Fitoterapia, 159:105201. https://doi.org/10.1016/j.fitote.2022.105201
Luo XW, Gao CH, Lu HM, et al., 2020. HPLC-DAD-guided isolation of diversified chaetoglobosins from the coral-associated fungus Chaetomium globosum C2F17. Molecules, 25(5):1237. https://doi.org/10.3390/molecules25051237
Luo XW, Cai GD, Guo YF, et al., 2021. Exploring marine-derived ascochlorins as novel human dihydroorotate dehydrogenase inhibitors for treatment of triple-negative breast cancer. J Med Chem, 64(18):13918–13932. https://doi.org/10.1021/acs.jmedchem.1c01402
Roux I, Woodcraft C, Hu JY, et al., 2020. CRISPR-mediated activation of biosynthetic gene clusters for bioactive molecule discovery in filamentous fungi. ACS Synth Biol, 9(7): 1843–1854. https://doi.org/10.1021/acssynbio.0c00197
Wang JM, Li ZC, Zhang YT, et al., 2022. A new α-cyclopiazonic acid alkaloid identified from the Weizhou Island coral-derived fungus Aspergillus flavus GXIMD 02503. J Ocean Univ China, 21(5):1307–1312. https://doi.org/10.1007/s11802-022-4959-5
Wang WQ, Tang KH, Wang PX, et al., 2022. The coral pathogen Vibrio coralliilyticus kills non-pathogenic holobiont competitors by triggering prophage induction. Nat Ecol Evol, 6(8):1132–1144. https://doi.org/10.1038/s41559-022-01795-y
Wu Q, Wu CM, Long HL, et al., 2015a. Varioxiranols A–G and 19-O-methyl-22-methoxypre-shamixanthone, PKS and hybrid PKS-derived metabolites from a sponge-associated Emericella variecolor fungus. J Nat Prod, 78(10):2461–2470. https://doi.org/10.1021/acs.jnatprod.5b00578
Wu Q, Long HL, Liu D, et al., 2015b. Varioxiranols I–L, new lactones from a sponge-associated Emericella variecolor fungus. J Asian Nat Prod Res, 17(12):1137–1145. https://doi.org/10.1080/10286020.2015.1119127
Zhang YT, Li ZC, Huang BY, et al., 2022. Anti-osteoclastogenic and antibacterial effects of chlorinated polyketides from the Beibu Gulf coral-derived fungus Aspergillus unguis GXIMD 02505. Mar Drugs, 20(3):178. https://doi.org/10.3390/md20030178
Zhou HB, Sun XH, Li N, et al., 2016. Isoindolone-containing meroperpenoids from the endophytic fungus Emericella nidulans HDN12-249. Org Lett, 18(18):4670–4673. https://doi.org/10.1021/acs.orglett.6b02297
Zhou XF, Liang Z, Li KL, et al., 2019. Exploring the natural piericidins as anti-renal cell carcinoma agents targeting peroxiredoxin 1. J Med Chem, 62(15):7058–7069. https://doi.org/10.1021/acs.jmedchem.9b00598
Zhu F, Lin YC, 2007. Three xanthones from a marine-derived mangrove endophytic fungus. Chem Nat Compd, 43(2):132–135. https://doi.org/10.1007/s10600-007-0062-9
Acknowledgments
This research was supported by the Guangxi Natural Science Foundation (Nos. 2020GXNSFBA159001, 2020GXNSF GA297002, and 2021GXNSFAA220052), the National Natural Science Foundation of China (Nos. U20A20101 and 22007019), the Special Fund for Bagui Scholars of Guangxi (Yonghong LIU), and the Scientific Research Foundation of Guangxi University of Chinese Medicine (No. 2022C038), China.
Author information
Authors and Affiliations
Corresponding author
Additional information
Materials and methods
Detailed methods are provided in the electronic supplementary materials of this paper.
Author contributions
Xiaowei LUO and Yonghong LIU conceived the research and designed experiments. Miaoping LIN, Zhenzhou TANG, Jiaxi WANG, Humu LU, Chenwei WANG, Yanting ZHANG, Xinming LIU, and Chenghai GAO performed the experiments and analysis. Xiaowei LUO, Miaoping LIN, and Zhenzhou TANG interpreted the data and wrote the paper. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
Compliance with ethics guidelines
Miaoping LIN, Zhenzhou TANG, Jiaxi WANG, Humu LU, Chenwei WANG, Yanting ZHANG, Xinming LIU, Chenghai GAO, Yonghong LIU, and Xiaowei LUO declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
Supplementary information
Materials and methods; Figs. S1–S9; Physicochemical data of known compounds 2–11
Supplementary information
11585_2023_685_MOESM1_ESM.pdf
An epipolythiodioxopiperazine alkaloid and diversified aromatic polyketides with cytotoxicity from the Beibu Gulf coral-derived fungus Emericella nidulans GXIMD 02509
Rights and permissions
About this article
Cite this article
Lin, M., Tang, Z., Wang, J. et al. An epipolythiodioxopiperazine alkaloid and diversified aromatic polyketides with cytotoxicity from the Beibu Gulf coral-derived fungus Emericella nidulans GXIMD 02509. J. Zhejiang Univ. Sci. B 24, 275–280 (2023). https://doi.org/10.1631/jzus.B2200622
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B2200622