Cytotoxic isocoumarin derivatives from the mangrove endophytic fungus Aspergillus sp. HN15-5D

  • Yingnan Wu
  • Senhua Chen
  • Hongju Liu
  • Xishan Huang
  • Yayue Liu
  • Yiwen Tao
  • Zhigang She
Research Article


Five isocoumarin derivatives including three new compounds, aspergisocoumrins A–C (13), together with two known analogues, 8-dihydroxyisocoumarin-3-carboxylic acid (4) and dichlorodiaportin (5) were obtained from the culture of the endophytic fungus Aspergillus sp. HN15-5D derived from the fresh leaves of the mangrove plant Acanthus ilicifolius. Their structures were elucidated using comprehensive spectroscopic methods. The double bond geometry of compounds 1 and 2 were assigned as E and Z on the basis of the distinct coupling constants, respectively. Compounds 1 and 2 showed cytotoxicity against MDA-MB-435 with IC50 values of 5.08 ± 0.88 and 4.98 ± 0.74 μM, respectively.


Isocoumarins Cytotoxicity Aspergillus sp. Mangrove endophytic fungus 



We thank the National Natural Science Foundation of China (21472251, 41404134), the Science & Technology Plan Project of Guangdong Province of China (2013B021100021), Natural Science Program of Guangdong Province (2016A030313588) and the Key Project of Natural Science Foundation of Guangdong Province (2016A040403091) for generous support.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

12272_2018_1019_MOESM1_ESM.docx (859 kb)
Supplementary material 1 (DOCX 858 kb)


  1. Abd El-Hady FK, Abdel-Aziz MS, Shaker KH, El-Shahid ZA, Ibrahim LS (2015) Antioxidant, acetylcholinesterase and α-glucosidase potentials of metabolites from the marine fungus Aspergillus unguis RSPG_204 associated with the sponge (Agelas sp.). Int J Pharm Sci Rev Res 30:272–278Google Scholar
  2. Chaiyosang B, Kanokmedhakul K, Boonmak J, Youngme S, Kukongviriyapan V, Soytong K, Kanokmedhakul S (2016) A new lumazine peptide penilumamide E from the fungus Aspergillus terreus. Nat Prod Res 30:1017–1024CrossRefPubMedGoogle Scholar
  3. Chen M, Shao CL, Wang KL, Xu Y, She ZG, Wang CY (2014) Dihydroisocoumarin derivatives with antifouling activities from a gorgonian-derived Eurotium sp. fungus. Tetrahedron 70:9132–9138CrossRefGoogle Scholar
  4. Chen S, Chen D, Cai R, Cui H, Long Y, Lu Y, Li C, She Z (2016a) Cytotoxic and antibacterial preussomerins from the mangrove endophytic fungus Lasiodiplodia theobromae ZJ-HQ1. J Nat Prod 79:2397–2402CrossRefPubMedGoogle Scholar
  5. Chen S, Liu Y, Liu Z, Cai R, Lu Y, Huang X, She Z (2016b) Isocoumarins and benzofurans from the mangrove endophytic fungus Talaromycesamestolkiae possess α-glucosidase inhibitory and antibacterial activities. RSC Adv 6:26412–26420CrossRefGoogle Scholar
  6. Cheng F, Deng Z, Guo Z, Chen J, Zou K (2013) Machilusmarin, a new neuroprotective isocoumarin dimer from the stems of Machilus ichangensis Rehd. et Wils. Nat Prod Res 27:1542–1547CrossRefPubMedGoogle Scholar
  7. Chinworrungsee M, Kittakoop P, Isaka M, Chanphen R, Tanticharoen M, Thebtaranonth Y (2002) Halorosellins A and B, unique isocoumarin glucosides from the marine fungus Halorosellinia oceanica. J Chem Soc Perkin Trans 1(22):2473–2476CrossRefGoogle Scholar
  8. Dai JR, Carté BK, Sidebottom PJ, Sek Yew AL, Ng SB, Huang Y, Butler MS, Circumdatin G (2001) A new alkaloid from the fungus Aspergillus ochraceus. J Nat Prod 64:125–126CrossRefPubMedGoogle Scholar
  9. Ellestad GA, Maurice Lovell F, Perkinson NA, Hargreaves RT, McGahren WJ (1978) New Zearalenone related macrolides and isocoumarins from an unidentified fungus. J Org Chem 43:2339–2343CrossRefGoogle Scholar
  10. Glauser G, Gindro K, Fringeli J, De Joffrey JP, Rudaz S, Wolfender JL (2009) Differential analysis of mycoalexins in confrontation zones of grapevine fungal pathogens by ultrahigh pressure liquid chromatography/time-of-flight mass spectrometry and capillary nuclear magnetic resonance. J Agr Food Chem 57:1127–1134CrossRefGoogle Scholar
  11. Hill RA (1986) Naturally occurring isocoumarins. In: Progress in the Chemistry of Organic Natural Products. Springer, Vienna, pp 1–78Google Scholar
  12. Huang HB, Feng XJ, Liu L, Chen B, Lu YJ, Ma L, She ZG, Lin YC (2010) Three dimeric naphtho-γ-pyrones from the mangrove endophytic fungus Aspergillus tubingensis isolated from pongamia pinnata. Planta Med 76:1888–1891CrossRefPubMedGoogle Scholar
  13. Huang J, Lu C, Qian X, Huang Y, Zheng Z, Shen Y (2011) Effect of salinity on the growth, biological activity and secondary metabolites of some marine fungi. Acta Oceanol Sin 30:118–123CrossRefGoogle Scholar
  14. Huang H, Wang F, Luo M, Chen Y, Song Y, Zhang W, Zhang S, Ju J (2012) Halogenated anthraquinones from the marine-derived fungus Aspergillussp.SCSIO F063. J Nat Prod 75:1346–1352CrossRefPubMedGoogle Scholar
  15. Huang X, Huang H, Li H, Sun X, Huang H, Lu Y, Lin Y, Long Y, She Z (2013) Asperterpenoid A, a new sesterterpenoid as an inhibitor of Mycobacterium tuberculosis protein tyrosine Phosphatase B from the culture of Aspergillus sp. 16-5c. Org Lett 15:721–723CrossRefPubMedGoogle Scholar
  16. Kito K, Ookura R, Yoshida S, Namikoshi M, Ooi T, Kusumi T (2008) New cytotoxic 14-membered macrolides from marine-derived fungus Aspergillus ostianus. Org Lett 10:225–228CrossRefPubMedGoogle Scholar
  17. Kwon-Chung KJ, Sugui JA (2013) Aspergillus fumigatus—what makes the species a ubiquitous human fungal pathogen? PLoS Pathog 9:e1003743CrossRefPubMedCentralPubMedGoogle Scholar
  18. Larsen TO, Breinholt J (1999) Dichlorodiaportin, diaportinol, and diaportinic acid: three novel isocoumarins from Penicillium nalgiovense. J Nat Prod 62:1182–1184CrossRefPubMedGoogle Scholar
  19. Le DH, Takenaka Y, Hamada N, Miyawaki H, Tanahashi T (2013) A 14-membered macrolide and isocoumarin derivatives from the cultured lichen mycobionts of Graphis vestitoides. Chem Pharm Bull 61:358–362CrossRefPubMedGoogle Scholar
  20. Li D, Xu Y, Shao CL, Yang RY, Zheng CJ, Chen YY, Fu XM, Qian PY, She ZG, Voogd NJ, Wang CY (2012) Antibacterial bisabolane-type sesquiterpenoids from the sponge-derived fungus Aspergillus sp. Mar Drugs 10:234–241CrossRefPubMedCentralPubMedGoogle Scholar
  21. Liang Z, Zhang T, Zhang X, Zhang J, Zhao C (2015) An alkaloid and a steroid from the endophytic fungus Aspergillus fumigatus. Molecules 20:1424–1433CrossRefPubMedGoogle Scholar
  22. Liao L, You M, Chung BK, Oh DC, Oh KB, Shin J (2015) Alkaloidal metabolites from a marine-derived Aspergillus sp. fungus. J Nat Prod 78:349–354CrossRefPubMedGoogle Scholar
  23. Liu Z, Chen Y, Chen S, Liu Y, Lu Y, Chen D, Lin Y, Huang X, She Z (2016) Aspterpenacids A and B, two sesterterpenoids from a mangrove endophytic fungus Aspergillus terreus H010. Org Lett 18:1406–1409CrossRefPubMedGoogle Scholar
  24. Nguyen VT, Lee JS, Qian ZJ, Li YX, Kim KN, Heo SJ, Jeon YJ, Park WS, Choi IW, Je JY, Jung WK (2013) Gliotoxin isolated from marine fungus Aspergillus sp. induces apoptosis of human cervical cancer and chondrosarcoma cells. Mar Drugs 12:69–87CrossRefPubMedCentralPubMedGoogle Scholar
  25. Nozawa K, Yamada M, Tsuda Y, Kawai K, Nakajima S (1981) Antifungal activity of oosponol, oospolactone, phyllodulcin, hydrangenol, and some other related compounds. Chem Pharm Bull 29:2689–2691CrossRefPubMedGoogle Scholar
  26. Pettit GR, Xu JP, Chapuis JC, Pettit RK, Tackett LP, Doubek DL, Hooper JNA, Schmidt JM (2004) Antineoplastic agents. 520. Isolation and structure of irciniastatins A and B from the indo-pacific marine sponge Ircinia ramosa 1. J Med Chem 47:1149–1152CrossRefGoogle Scholar
  27. Prompanya C, Dethoup T, Bessa LJ, Pinto MMM, Gales L, Costa PM, Silva AMS, Kijjoa A (2014) New isocoumarin derivatives and meroterpenoids from the marine sponge-associated fungus Aspergillus similanensis sp. nov. KUFA 0013. Mar Drugs 12:5160–5173CrossRefPubMedCentralPubMedGoogle Scholar
  28. Saeed A (2016) Isocoumarins, miraculous natural products blessed with diverse pharmacological activities. Eur J Med Chem 116:290–317CrossRefPubMedGoogle Scholar
  29. Sun K, Li Y, Guo L, Wang Y, Liu P, Zhu W (2014) Indole diterpenoids and isocoumarin from the fungus, Aspergillus flavus, isolated from the prawn, Penaeus vannamei. Mar Drugs 12:3970–3981CrossRefPubMedCentralPubMedGoogle Scholar
  30. Volke-Sepulveda T, Salgado-Bautista D, Bergmann C, Wells L, Gutierrezsanchez G, Favelatorres E (2016) Secretomic insight into glucose metabolism of Aspergillus brasiliensis in solid-state fermentation. J Proteome Res 15:3856–3871CrossRefPubMedGoogle Scholar
  31. Wei MY, Wang CY, Liu QA, Shao CL, She ZG, Lin YC (2010) Five sesquiterpenoids from a marine-derived fungus Aspergillus sp. isolated from a gorgonian Dichotella gemmacea. Mar Drugs 8:941–949CrossRefPubMedCentralPubMedGoogle Scholar
  32. Xiao Z, Huang H, Shao C, Xia X, Ma L, Huang X, Lu Y, Lin Y, Long Y, She Z (2013) Asperterpenols A and B, new sesterterpenoids isolated from a mangrove endophytic fungus Aspergillus sp. 085242. Org Lett 15:2522–2525CrossRefPubMedGoogle Scholar
  33. Zhao Y, Liu D, Proksch P, Yu S, Lin W (2016) Isocoumarin derivatives from the sponge-associated fungus Peyronellaea glomerata with antioxidant activities. Chem Biodivers 13:1186–1193CrossRefPubMedGoogle Scholar
  34. Zhuang Y, Teng X, Wang Y, Liu P, Li G, Zhu W (2011) New quinazolinone alkaloids within rare amino acid residue from coral-associated fungus, Aspergillus versicolor LCJ-5-4. Org Lett 13:1130–1133CrossRefPubMedGoogle Scholar
  35. Zhuravleva OI, Afiyatullov SS, Denisenko VA, Ermakova SP, Slinkina NN, Dmitrenok PS, Kim NY (2012) Secondary metabolites from a marine-derived fungus Aspergillus carneus Blochwitz. Phytochemistry 80:123–131CrossRefPubMedGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2018

Authors and Affiliations

  1. 1.School of ChemistrySun Yat-Sen UniversityGuangzhouChina
  2. 2.College of Food Science and TechnologyGuangdong Ocean UniversityZhanjiangChina
  3. 3.South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation CenterGuangzhouChina

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