内生真菌Periconia sp. F-31中的三个新化合物

doi:10.5246/jcps.2020.04.023

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (4): 244-251.DOI: 10.5246/jcps.2020.04.023

内生真菌Periconia sp. F-31中的三个新化合物

刘继梅¹, 陈明华², 陈日道¹, 解可波¹, 陈大伟¹, 司书毅², 戴均贵^1*

1. 中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室; 酶与药用天然产物生物催化中国医学科学院重点实验室; 天然药物生物合成卫建委重点实验室, 北京 100050
2. 中国医学科学院北京协和医学院医药生物技术研究所微生物药物生物工程卫建委重点实验室, 北京 100050

收稿日期:2019-12-20 修回日期:2020-01-25 出版日期:2020-04-30 发布日期:2020-03-22
通讯作者: Tel.: +86-10-63165195, E-mail: jgdai@imm.ac.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81773607), CAMS Innovation Fund for Medical Sciences (Grant Nos. CIFMS-2018-I2M-3-005 and CIFMS-2016-I2M-2-002), the Drug Innovation Major Project (Grant No. 2018ZX09711001-001-001).

Three new compounds from endophytic fungus Periconia sp. F-31

Jimei Liu¹, Minghua Chen², Ridao Chen¹, Kebo Xie¹, Dawei Chen¹, Shuyi Si², Jungui Dai^1*

1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines; CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs; and NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
2. NHC Key Laboratory for Microbial Drug Bioengeering, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

Received:2019-12-20 Revised:2020-01-25 Online:2020-04-30 Published:2020-03-22
Contact: Tel.: +86-10-63165195, E-mail: jgdai@imm.ac.cn
Supported by:
National Natural Science Foundation of China (Grant No. 81773607), CAMS Innovation Fund for Medical Sciences (Grant Nos. CIFMS-2018-I2M-3-005 and CIFMS-2016-I2M-2-002), the Drug Innovation Major Project (Grant No. 2018ZX09711001-001-001).

摘要/Abstract

摘要：

从番荔枝内生真菌Periconia sp. F-31的次生代谢产物中分离得到3个新化合物, 通过多种波谱学方法及计算ECD鉴定了所分离化合物的结构, 分别为二氯取代的异香豆素pericochlorosin A (1)、含氯取代苯酚化合物pericochlorosin B (2)和十氢化萘衍生物pericoannosin G (3)。药理活性评价表明, 化合物2具有较强的抗HIV活性, 其IC₅₀为2.2 μM。

关键词: 内生真菌, 黑团孢霉属, Pericochlorosin, Pericoannosin

Abstract:

Three new compounds (1–3), includinga chlorine-containing dihydroisocoumarin pericochlorosin A (1), a chlorinated phenol pericochlorosin B (2) and a decalin derivative pericoannosin G (3), were isolated from endophytic fungus Periconia sp. F-31 of the medicinal plant Annona muricata. The structures and absolute configurations were elucidated by extensive spectroscopic methods and calculated electronic circular dichroism analysis. Compound 2 displayed potent anti-HIV activity with IC₅₀ value of 2.2 μM.

Key words: Endophytic fungus, Periconia, Pericochlorosin, Pericoannosin

中图分类号:

R284

Supporting:

1. ECD and OR Calculations of 3

Since the relative configuration of 3 was established by the NOESY spectrum, only two stereoisomers existed: (2R, 3S, 8S, 11R)-3a and (2S, 3R, 8R, 11S)-3b(Figure S1). Conformational analysis of 3a was carried out via Monte Carlo searching with the MMFF94 molecular mechanics force field using the Spartan14 software.¹ Conformational analyses of 3a showed 4 conformers having relative energy within 10 kcal/mol were considered for further DFT calculations at B3LYP/6-31+G (d, p) level in methanol (Figure S2). Subsequently, the conformers were re-optimized using DFT at the WB97XD/DGDZVP level in methanol with the Gaussian 09 program.² (Tables S1). The WB97XD/DGDZVP harmonic vibrational frequencies were further calculated to confirm their stability. Those stable conformers with their Boltzmann distribution (>1%) also were carried out at the TDDFT CAM-B3LYP/DGDZVP, and B3LYP/6-311++G (2d, p) level in the methanol for ECD and OR computation, respectively. Boltzmann statistics were performed for ECD simulations with a standard deviation of σ 0.3 Ev. The final ECD spectra and OR value of 3a were obtained according to the Boltzmann distribution theory and their relative Gibbs free energy (ΔG), respectively. In the region of 200–400 nm, the theoretically calculated ECD spectrum of 3a was agreed with the experimental ECD spectrum of 3 (Figure S2). The experimental OR value of 3 (+15.0) was in good agreement with the theoretically calculated OR value of 3a (+194.4, Table S2) but was opposite in sign to that of 3b (–194.4) in methanol.

Figure S1. The structure of 3 (3a and 3b)

Figure S2. WB97XD/DGDZVP optimized 4 lowest energy 3D conformers of 3a

Table S1.Free energies (ΔG), and Boltzmann distribution abundances of conformers of 3a

Table S2. Calculated OR Values of the Lowest Energy Conformers of 3a.

^aAveraged according to the Boltzmann-calculated contribution at WB97XD/DGDZVP level.

References

(1) Spartan 14, Wavefunction, Inc.: Irvine, CA.

(2) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision C.01; Gaussian, Inc., Wallingford CT, 2010.

2. NMR, MS, IR, UV, CD spectra of compounds 1–3

Figure S3. ¹H NMR spectrum of compound 1.

Figure S4. ¹³C NMR spectrum of compound 1.

Figure S5. DEPT spectrum of compound 1.

Figure S6. HSQC spectrum of compound 1.

Figure S7. HMBC spectrum of compound 1.

Figure S8. ESIMS spectrum of compound 1.

Figure S9. HRESIMS spectrum of compound 1.

Figure S10. IR spectrum of compound 1.

Figure S11. UV spectrum of compound 1.

Figure S12. ECD spectrum of compound 1

Figure S13. ¹H NMR spectrum of compound 2.

Figure S14. ¹³C NMR spectrum of compound 2.

Figure S15. DEPT spectrum of compound 2.

Figure S16. HSQC spectrum of compound 2.

Figure S17. HMBC spectrum of compound 2.

Figure S18. ESIMS spectrum of compound 2.

Figure S19. HRESIMS spectrum of compound 2.

Figure S20. IR spectrum of compound 2.

Figure S21. UV spectrum of compound 2.

Figure S22. ECD spectrum of compound 2.

Figure S23. ¹H NMR spectrum of compound 3.

Figure S24. ¹³C NMR spectrum of compound 3.

Figure S25. DEPT spectrum of compound 3.

Figure S26. HSQC spectrum of compound 3.

Figure S27. ¹H-¹H COSY spectrum of compound 3.

Figure S28. HMBC spectrum of compound 3.

Figure S29. 1D-NOE spectrum of compound 3.

Figure S30. NOESY spectrum of compound 3.

Figure S31. HRESIMS spectrum of compound 3.

Figure S32. IR spectrum of compound 3.

Figure S33. UV spectrum of compound 3.

Figure S34. ECD spectrum of compound 3.

刘继梅, 陈明华, 陈日道, 解可波, 陈大伟, 司书毅, 戴均贵. 内生真菌Periconia sp. F-31中的三个新化合物[J]. 中国药学(英文版), 2020, 29(4): 244-251.

Jimei Liu, Minghua Chen, Ridao Chen, Kebo Xie, Dawei Chen, Shuyi Si, Jungui Dai. Three new compounds from endophytic fungus Periconia sp. F-31[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(4): 244-251.

参考文献

[1] Schulz, B.; Boyle, C.; Draeger, S.; Römmert, A.K.; Krohn, K. Endophytic fungi: a source of novel biologically active secondary metabolites. Mycol. Res. 2002, 106, 996-1004.

[2] Kharwar, R.N.; Mishra, A.; Gond, S.K.; Stierle, A.; Stierle, D. Anticancer compounds derived from fungal endophytes: their importance and future challenges. Nat. Prod. Rep. 2011, 28, 1208-1228.

[3] Gubiani, J.R.; Zeraik, M.L.; Oliveira, C.M.; Ximenes, V.F.; Nogueira, C.R.; Fonseca, L.M.; Silva, D.H.; Bolzani, V.S.; Araujo, A.R. Biologically active eremophilane-type sesquiterpenes from Camarops sp., an endophytic fungus isolated from Alibertia macrophylla. J. Nat. Prod. 2014, 77, 668-672.

[4] Liu, Y.B.; Li, Y.; Qu, J.; Ma, S.G.; Zang, C.X.; Zhang, Y.T.; Yu, S.S. Eremophilane sesquiterpenes and polyketones produced by an endophytic Guignardia fungus from the toxic plant Gelsemium elegans. J. Nat. Prod. 2015, 78, 2149-2154.

[5] He, W.W.; Xu, Y.C.; Fu, P.; Zuo, M.X.; Liu, W.; Jiang, Y.M.; Wang, L.P.; Zhu, W.M. Cytotoxic indolyl diketopiperazines from the Aspergillus sp. GZWMJZ-258, endophytic with the medicinal and edible plant Garcinia multiflora. J. Agric. Food Chem. 2019, 67, 10660-10666.

[6] Wu, J.C.; Hou, Y.N.; Xu, Q.H.; Jin, X.J.; Chen, Y.X.; Fang, J.G.; Hu, B.R.; Wu, Q.X. (±)-alternamgin, a pair of enantiomeric polyketides, from the endophytic fungi Alternaria sp. MG1. Org. Lett. 2019, 21, 1551-1554.

[7] Yang, H.X.; Ai, H.L.; Feng, T.; Wang, W.X.; Wu, B.; Zheng, Y.S.; Sun, H.; He, J.; Li, Z.H.; Liu, J.K. Trichothecrotocins A-C, antiphytopathogenic agents from potato endophytic fungus Trichothecium crotocinigenum. Org. Lett. 2018, 20, 8069-8072.

[8] Zhang, D.W.; Ge, H.L.; Xie, D.; Chen, R.D.; Zou, J.H.; Tao, X.Y.; Dai, J.G. Periconiasins A-C, new cytotoxic cytochalasans with an unprecedented 9/6/5 tricyclic ring system from endophytic fungus Periconia sp. Org. Lett. 2013, 15, 1674-1677.

[9] Zhang, D.W.; Ge, H.L.; Zou, J.H.; Tao, X.Y.; Chen, R.D.; Dai, J.G. Periconianone A, a new 6/6/6 carbocyclic sesquiterpenoid from endophytic fungus Periconia sp. with neural anti-inflammatory activity. Org. Lett. 2014, 16, 1410-1413.

[10] Zhang, D.W.; Tao, X.Y.; Chen, R.D.; Liu, J.M.; Li, L.; Fang, X.M.; Yu, L.Y.; Dai, J.G. Pericoannosin A, a polyketide synthase-nonribosomal peptide synthetase hybrid metabolite with new carbon skeleton from the endophytic fungus Periconia sp. Org. Lett. 2015, 17, 4304-4307.

[11] Liu, J.M.; Zhang, D.W.; Zhang, M.; Zhao, J.L.; Chen, R.D.; Wang, N.; Zhang, D.; Dai, J.G. Eremophilane sesquiterpenes from an endophytic fungus Periconia species. J. Nat. Prod. 2016, 79, 2229-2235.

[12] Liu, J.M.; Zhang, D.W.; Zhang, M.; Liu, X.; Chen, R.D.; Zhao, J.L.; Li, Wang, N.; Dai, J.G. Periconiasins I and J, two new cytochalasans from an endophytic fungus Periconia sp. Tetrahedron Lett. 2016, 57, 5794-5797.

[13] Liu, J.M.; Zhang, D.W.; Zhang, M.; Chen, R.D.; Yan, Z.; Zhao, J.Y.; Zhao, J.L.; Wang, N.; Dai, J.G. Periconones B-E, new meroterpenoids from endophytic fungus Periconia sp. Chin. Chem. Lett. 2017, 28, 248-252.

[14] Liu, J.M.; Zhang, D.W.; Du, W.Y.; Zhang, M.; Zhao, J.L.; Chen, R.D.; Xie, K.B.; Dai, J.G. Four new monoterpenoids from an endophytic fungus Periconia sp. F-31. J. Asian. Nat. Prod. Res. 2017, 19, 541-549.

[15] Fan, Y.J.; Zhang, D.W.; Tao, X.Y.; Wang, Y.H.; Liu, J.M.; Li, L.; Zhao, J.Y.; Yu, L.Y.; He, Y.P.; Dai, J.G.; Tang, Y.F. Biosynthetic hypothesis-guided discovery and total syntheses of PKS-NRPS hybrid metabolites from endophytic fungus Periconia species. Org. Lett. 2019, 21, 1794-1798.

[16] Carmichael, J.; DeGraff, W.G.; Gazdar, A.F.; Minna, J.D.; Mitchell, J.B. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 1987, 47, 936-942.

[17] Zhang, Q.; Liu, Z.L.; Mi, Z.Y.; Li, X.Y.; Jia, P.P.; Zhou, J.M.; Yin, X.; You, X.F.; Yu, L.Y.; Guo, F.; Ma, J.; Liang, C.; Cen, S. High-throughput assay to identify inhibitors of Vpu-mediated down-regulation of cell surface BST-2. Antiviral Res. 2011, 91, 321-329.

[18] Krohn, K.; Bahramsari, R.; Flörke, U.; Ludewig, K.; Kliche-Spory, C.; Michel, A.; Aust, H.J.; Draeger, S.; Schulz, B.; Antus, S. Dihydroisocoumarins from fungi: isolation, structure elucidation, circular dichroism and biological activity. Phytochemistry. 1997, 45, 313-320.

[19] Henderson, G.B.; Hill, R.A. Synthesis of chlorinated isocoumarin derivatives. J. Chem. Soc. Perkin Trans. 1982, 1, 1111-1115.

[20] Giles, D.; Turner, W.B. Chlorine-containing metabolites of Periconia macrospinosa. J. Chem. Soc. Perkin Trans. 1969, 16, 2187-2189.

内生真菌Periconia sp. F-31中的三个新化合物

Three new compounds from endophytic fungus Periconia sp. F-31

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 5

编辑推荐

Metrics

本文评价

[1]	赵爱红, 王天霞, 刘晓艳, 赵伟红, 马建苹, 杨秀伟, 郭涛, 张友波. 竹叶椒抗炎内生真菌的分离[J]. 中国药学(英文版), 2021, 30(7): 570-577.
[2]	乔自鹏, 王奇志, 刘建福, 王明元. 胜红蓟内生真菌乙酸乙酯提取物的抗氧化及抑菌活性研究[J]. 中国药学(英文版), 2021, 30(5): 421-433.
[3]	梁晓霞, 熊城, 高迎迎, 范巧佳. 天麻内生真菌提取物抗氧化活性及天麻素的测定[J]. 中国药学(英文版), 2020, 29(3): 206-213.
[4]	陈楠, 梁晓霞. 紫花玉簪内生真菌分离鉴定及其抗氧化活性研究[J]. 中国药学(英文版), 2018, 27(10): 711-718.
[5]	杨登峰, 刘凤楼, 杨小龙. DNA甲基转移酶抑制剂改变小孢拟盘多毛孢次级代谢产物的研究[J]. 中国药学(英文版), 2017, 26(5): 355-359.