Planta Med 2023; 89(03): 295-307
DOI: 10.1055/a-1917-7910
Biological and Pharmacological Activity
Original Papers

Antimicrobial Acylphloroglucinol Meroterpenoids and Acylphloroglucinols from Dryopteris crassirhizoma

Ping Hai
1   Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
Yunqing He
2   Faculty of Materials and Chemical Engineering, Yibin University, Yibin, China
Ruirui Wang
3   School of Pharmaceutical Sciences, Yunnan University of Chinese Medicine, Kunming, China
Jian Yang
4   State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medical, China Academy of Chinese Medical Sciences, Beijing, China
Yuan Gao
2   Faculty of Materials and Chemical Engineering, Yibin University, Yibin, China
Xudong Wu
2   Faculty of Materials and Chemical Engineering, Yibin University, Yibin, China
Nie Chen
2   Faculty of Materials and Chemical Engineering, Yibin University, Yibin, China
Li Ye
2   Faculty of Materials and Chemical Engineering, Yibin University, Yibin, China
Rongtao Li
1   Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China
› Author Affiliations
Supported by: the Key Project at Central Government Level: the ability establishment of sustainable use for valuable Chinese medicine resources 2060302
Supported by: the Scientific and technological innovation project of China Academy of Chinese Medical Sciences CI2021A01809
Supported by: the Scientific and technological innovation project of China Academy of Chinese Medical Sciences CI2021A04005
Supported by: the Fundamental Research Funds for the Central public welfare research institutes ZZXT201906
Supported by: the Startup Project supported by Yibin University 2021QH03
Supported by: National Natural Science Foundation of China 21702181
Supported by: National Natural Science Foundation of China 22067012
Supported by: National Natural Science Foundation of China 82060637
Supported by: the Yunnan Innovation Team, the Higher Educational Key Laboratory for New drugs for Viral Respiratory Diseases (Chinese Traditional Medicine) of Yunnan Province 2019HC018
Supported by: the Key Lab of Process Analysis and Control of Sichuan Universities GCFX2021004


Ten novel meroterpenoids, dryoptins/11″-epi-dryoptins A~E (1~10) with an unprecedented skeleton consisting of dimeric or trimeric acylphloroglucinols and dehydrotheonelline, two undescribed acylphloroglucinol-nerolidol meroterpenoids (11~12), and ten known acylphloroglucinol derivatives (13~22), were isolated from D. crassirhizoma. The novel structures including absolute configurations were established by comprehensive spectroscopic analyses and quantum chemical electronic circular dichroism (ECD) calculations. A biosynthetic pathway of 1~10 was assumed. The trimeric acylphloroglucinol meroterpenoids 7/8 showed significant antifungal activity against standard Candida albicans with a MIC50 value of 1.61 µg/mL [fluconazole (FLC): 3.41 µg/mL], and when combined with FLC, the principal components 20 and 21 exhibited strong antifungal activities against FLC-resistant C. albicans with MIC50 values of 8.39 and 7.16 µg/mL (FLC: > 100 µg/mL), respectively. Moreover, compounds 2, 5/6, 18, 19, and 21 exhibited inhibitory effects against several pathogenic fungi and bacteria, with MIC50 values of 6.25 ~ 50 µg/mL.

Supporting Information

Publication History

Received: 06 March 2022

Accepted after revision: 03 August 2022

Accepted Manuscript online:
03 August 2022

Article published online:
08 December 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Zhang LB. Flora of China. Beijing: Science Press; 2013: 5714
  • 2 Lian YQ, Wang XN, Chen ZC, Liu BD. Studies on the using of Dryopteris crassirhizoma Nakai. Zhongguo yesheng zhiwu ziyuan 2005; 24: 29-32
  • 3 Chen X, Wu Y, Chen C, Gu Y, Zhu C, Wang S, Chen J, Zhang L, Lv L, Zhang G, Yuan Y, Chai Y, Zhu M, Wu C. Identifying potential anti-COVID-19 pharmacological components of traditional Chinese medicine Lianhuaqingwen capsule based on human exposure and ACE2 biochromatography screening. Acta Pharm Sin B 2021; 11: 222-236
  • 4 Yu BF, Zheng X, Ni YF. Observation on the curative effect of Kang gan ke li in the treatment of 62 children with acute upper respiratory tract infection. West China J Pharm Sciences 2008; 23: 732
  • 5 Chen N, Wu Z, Li W, Li Y, Luo D, Chen L, Zhang X, Zhang Y, Guocai W, Li Y. Acylphloroglucinols-based meroterpenoid enantiomers with antiviral activities from Dryopteris crassirhizoma . Ind Crop Prod 2020; 150: 112415
  • 6 Ban SH, Kim JE, Pandit S, Jeon JG. Influences of Dryopteris crassirhizoma extract on the viability, growth and virulence properties of Streptococcus mutans . Molecules 2012; 17: 9231-9244
  • 7 Wang J, Yan YT, Fu SZ, Peng B, Bao LL, Zhang YL, Hu JH, Zeng ZP, Geng DH, Gao ZP. Anti-influenza virus (H5N1) activity screening on the phloroglucinols from rhizomes of Dryopteris crassirhizoma . Molecules 2017; 22: 431
  • 8 Hou B, Liu Z, Yang XB, Zhu WF, Li JY, Yang L, Reng FC, Lv YF, Hu JM, Liao GY, Zhou J. Total synthesis of dryocrassin ABBA and its analogues with potential inhibitory activity against drug-resistant neuraminidases. Bioorg Med Chem 2019; 27: 3846-3852
  • 9 Yim NH, Lee JJ, Lee B, Li W, Ma JY. Antiplatelet activity of acylphloroglucinol derivatives isolated from Dryopteris crassirhizoma . Molecules 2019; 24: 2212-2222
  • 10 Hai P, Rao K, Jiang N, Liu D, Wang R, Gao Y, Liu X, Deng S, Zhou Y, Chen X, Li X, Li R. Structure elucidation, biogenesis, and bioactivities of acylphloroglucinol-derived meroterpenoid enantiomers from Dryopteris crassirhizoma . Bioorg Chem 2022; 119: 105567
  • 11 Chen N, Li W, Zhang J, Xu W, Wu Z, Li Y, Zhang Y, Zhang Q, Wang G. Isolation and structural elucidation of β-tocopherol derivatives from Dryopteris crassirhizoma . Ind Crop Prod 2021; 172: 114010
  • 12 Ng KP, Kuan CS, Kaur H, Na SL, Atiya N, Velayuthan RD. Candida species epidemiology 2000–2013: a laboratory-based report. Trop Med Int Health 2015; 20: 1447-1453
  • 13 Pu D, Li X, Lin J, Zhang R, Luo T, Wang Y, Gao J, Zeb MA, Zhang X, Li X, Wang R, Xiao W. Triterpenoids from Ganoderma gibbosum: a class of sensitizers of FLC-resistant Candida albicans to fluconazole. J Nat Prod 2019; 82: 2067-2077
  • 14 Nidhi P, Rolta R, Kumar V, Dev K, Sourirajan A. Synergistic potential of Citrus aurantium L. essential oil with antibiotics against Candida albicans . J Ethnopharmacol 2020; 262: 113135
  • 15 Ito H, Muranaka T, Mori K, Jin ZX, Tokuda H, Nishino H, Yoshida T. Ichthyotoxic phloroglucinol derivatives from Dryopteris fragrans and their anti-tumor promoting activity. Chem Pharm Bull (Tokyo) 2000; 48: 1190-1195
  • 16 Ccana-Ccapatinta GV, Correa de Barros FM, Bridi H. Dimeric acylphloroglucinols in Hypericum species from sections Brathys and Trigynobrathys . Phytochem Rev 2014; 14: 25-50
  • 17 Na M, Jang J, Min BS, Lee SJ, Lee MS, Kim BY, Oh WK, Ahn JS. Fatty acid synthase inhibitory activity of acylphloroglucinols isolated from Dryopteris crassirhizoma . Bioorg Med Chem Lett 2006; 16: 4738-4742
  • 18 Patama TT, Widen CJ. Phloroglucinol derivatives from Dryopteris fusco-atra and D. hawaiiensis . Phytochemistry 1991; 30: 3305-3310
  • 19 Jia XZ, Li XX, Yuan LB, Yin YQ, Yang XH, Shen ZB. Study on the three kinds of phloroglucinol derivatives of Dryopteris crassirhizoma Nakai and their antifungal activity. J Guangdong Pharm Univ 2016; 32: 582-585
  • 20 Zhao DD, Zhao QS, Liu L, Chen ZQ, Zeng WM, Lei H, Zhang YL. Compounds from Dryopteris fragrans (L.) Schott with cytotoxic activity. Molecules 2014; 19: 3345-3355
  • 21 Tanaka N, Maehashi H, Saito S, Murakami T, Saiki Y, Chen G, Iitaka Y. Chemical and chemotaxonomical studies of ferns. XXXI. Chemical studies on the constituents of Arachinoides standishii Ohwi. Chem Pharm Bull 1980; 28: 3070-3077
  • 22 Ito H, Midori T, Mori K, Jin ZX, Yoshida T. Dryofragin and aspidin PB, piscicidal components from Dryopteris fragrans . Chem Pharm Bull 1997; 45: 1720-1722
  • 23 Zdero C, Lehmann L, Bohlmann F. Chemotaxonomy of Athanasia and related genera. Phytochemistry 1991; 30: 1161-1163
  • 24 Gao ZP, Ali Z, Zhao JP, Qiao L, Lei HM, Lu YR, Ikhlas AK. Phytochemical investigation of the rhizomes of Dryopteris crassirhizoma . Phytochem Lett 2008; 1: 188-190
  • 25 Bifulco G, Dambruoso P, Gomez-Paloma L, Riccio R. Determination of relative configuration in organic compounds by NMR spectroscopy and computational methods. Chem Rev 2007; 107: 3744-3779
  • 26 Gao ZP, Li RF, Wang BH, Lu RW. Progress in chemical constituents of genus Dryopteris. Chin. J Experimental Traditional Med Formulae 2003; 9: 50-55
  • 27 Van De Water RW, Pettus TRR. o-Quinone methides: intermediates underdeveloped and underutilized in organic synthesis. Tetrahedron 2002; 58: 5367-5405
  • 28 Lam HC, Spence JT, George JH. Biomimetic total synthesis of hyperjapones A–E and hyperjaponols A and C. Angew Chem Int Ed Engl 2016; 55: 10368-10371
  • 29 CLSI. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard – Third Edition. CLSI document M27-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2008
  • 30 Liu Y, Ren H, Wang D, Zhang M, Sun S, Zhao Y. The synergistic antifungal effects of gypenosides combined with fluconazole against resistant Candida albicans via inhibiting the drug efflux and biofilm formation. Biomed Pharmacother 2020; 130: 110580
  • 31 Zhao W, Xu LL, Zhang X, Gong XW, Zhu DL, Xu XH, Wang F, Yang XL. Three new phenanthrenes with antimicrobial activities from the aerial parts of Juncus effuses . Fitoterapia 2018; 130: 247-250