Skip to main content

Advertisement

Log in

Bioactive compounds of Aspergillus terreus—F7, an endophytic fungus from Hyptis suaveolens (L.) Poit

  • Original Paper
  • Published:
World Journal of Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

The compounds terrein (1), butyrolactone I (2), and butyrolactone V (3) were isolated from the ethyl acetate extract (EtOAc) of the endophytic fungus Aspergillus terreus—F7 obtained from Hyptis suaveolens (L.) Poit. The extract and the compounds presented schistosomicidal activity against Schistosoma mansoni; at 100 µg/mL for EtOAc extract, 1297.3 µM for compound 1, 235.6 µM for compound 2, and 454.1 µM for compound 3, they killed 100% of the parasites after 72 h of treatment. Compounds 1, 2, and 3 exerted moderate leishmanicidal activity against Leishmania amazonensis (IC50 ranged from 23.7 to 78.6 µM). At 235.6 and 227.0 µM, compounds 2 and 3, respectively, scavenged 95.92 and 95.12% of the DPPH radical (2,2-diphenyl-1-picryl-hydrazyl), respectively. Regarding the cytotoxicity against the breast tumor cell lines MDA-MB-231 and MCF-7, compound 2 gave IC50 of 34.4 and 17.4 µM, respectively, while compound 3 afforded IC50 of 22.2 and 31.9 µM, respectively. At 117.6 µM, compound 2 inhibited the growth of and killed the pathogen Escherichia coli (ATCC 25922). Compounds 1, 2, and 3 displayed low toxicity against the normal line of human lung fibroblasts (GM07492A cells), with IC50 of 15.3 × 103, 3.4 × 103, and 5.8 × 103 µM, respectively. This is the first report on (i) the in vitro schistosomicidal and leishmanicidal activities of the EtOAc extract of A. terreus—F7 and compounds 1, 2, and 3; and (ii) the antitumor activity of compounds 2 and 3 against MDA-MB-231 and MCF-7 cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Barton DHR, Miller E (1955) The constitution and stereochemistry of terrein. J Chem Soc 1028–1029. doi:10.1039/JR9550001028

  • Birch AJ, Cassera A, Jones AR (1965) The biosynthesis of terrein. Chem Commun 9:167–168

    Google Scholar 

  • Brewer MS (2011) Natural antioxidants: sources, compounds, mechanisms of action, and potential applications. Compr Rev Food Sci Food Saf 10:221–247

    Article  CAS  Google Scholar 

  • Calcul L, Waterman C, Ma WS, Lebar MD, Harter C, Mutka T, Morton L, Maignan P, Olphen AV, Kyle DE, Vrijmoed L, Pang K-L, Pearce C, Baker BJ (2013) Screening mangrove endophytic fungi for antimalarial natural products. Mar Drugs 11:5036–5050

    Article  CAS  Google Scholar 

  • Campos FF, Sales Junior PA, Romanha AJ, Araújo MS, Siqueira EP, Resende JM, Alves TM, Martins-Filho OA, Santos VL, Rosa CA, Zani CL, Cota BB (2015) Bioactive endophytic fungi isolated from Caesalpinia echinata Lam. (Brazilwood) and identification of beauvericin as a trypanocidal metabolite from Fusarium sp. Mem Inst Oswaldo Cruz 110:65–74

    Article  Google Scholar 

  • Cazar ME, Schmeda-Hirschmann G, Astudillo L (2005) Antimicrobial butyrolactone I derivatives from the Ecuadorian soil fungus Aspergillus terreus Thorn. var terreus. World J Microbiol Biotechnol 21:1067–1075

    Article  CAS  Google Scholar 

  • Cheung LM, Cheung PCK, Ooi VEC (2003) Antioxidant activity and total phenolics of edible mushroom extracts. Food Chem 81:249–255

    Article  CAS  Google Scholar 

  • Dewi RT, Tachibana S, Darmawan A (2012) Antidiabetic and antioxidative activities of butyrolactone I from Aspergillus terreus. WASET 6:818–823

    Google Scholar 

  • Dewi RT, Tachibana S, Darmawan A (2014) Effect on β-glucosidase inhibition and antioxidant activities of butyrolactone derivatives from Aspergillus terreus MC751. Med Chem Res 23:454–460

    Article  CAS  Google Scholar 

  • Garson MJ, Hill RA, Staunton J (1977) Deuterium as a tracer in polyketide biosynthesis: incorporation of [2-13C, 2-2H3] acetate into terrein. J Chem Soc Chem Commun 18:624–626

    Article  Google Scholar 

  • Goupil LS, McKerrow JH (2014) Introduction: drug discovery and development for neglected diseases. Chem Rev 114:11131–11137

    Article  CAS  Google Scholar 

  • Grove JF (1954) The structure of terrein. J Chem Soc 4693–4694

  • Guo F, Li Z, Xu X, Wang K, Shao M, Zhao F, Wang H, Hua H, Pei Y, Bai J (2016) Butenolide derivatives from the plant endophytic fungus Aspergillus terreus. Fitoterapia 113:44–50

    Article  CAS  Google Scholar 

  • Haritakun R, Rachtawee P, Chanthaket R, Boonyuen N, Isaka M (2010) Butyrolactones from the fungus Aspergillus terreus BCC 4651. Chem Pharm Bull 58:1545–1548

    Article  CAS  Google Scholar 

  • Haroon MH, Premaratne SR, Choudhry MI, Dharmaratne HR (2012) A new β-glucuronidase inhibiting butyrolactone from the marine endophytic fungus Aspergillus terreus. Nat Prod Res 27:1060–1066

    Article  Google Scholar 

  • Hormazabal E, Schmeda-Hirschmann G, Astudillo L, Rodríguez J, Theoduloz C (2005) Metabolites from Microsphaeropsis olivacea, an endophytic fungus of Pilgerodendron uviferum. Z Naturforsch, C. J Biosci 60:11–21

    CAS  Google Scholar 

  • Jayanthi G, Kamalraja S, Karthikeyanb K, Muthumarya J (2011) Antimicrobial and antioxidant activity of the endophytic fungus Phomopsis sp. GJJM07 isolated from Mesua ferrea. Int J Curr Sci 1:85–90

    Google Scholar 

  • Jouda JB, Kusari S, Lamshöft M, Mouafo TF, Douala MC, Wandji J, Spiteller M (2014) Penialidins A–C with strong antibacterial activities from Penicillium sp., an endophytic fungus harboring leaves of Garcinia nobilis. Fitoterapia 98:209–214

    Article  CAS  Google Scholar 

  • Kiriyama N, Sakaguchi Y, Taguchi Y, Yamamoto Y (1977) Studies on the metabolic products of Aspergillus terreus. III. Metabolites of the strain IFO 8835. Chem Pharm Bull 25:2593–2601

    Article  CAS  Google Scholar 

  • Kusari S, Lamshöft M, Zühlke S, Spiteller M (2008) An endophytic fungus from Hypericum perforatum that produces hypericin. J Nat Prod 71:26–29

    Article  Google Scholar 

  • Kusari S, Verma VC, Lamshoeft M, Spiteller M (2012) An endophytic fungus from Azadirachta indica A. Juss that produces azadirachtin. World J Microbiol Biotechnol 28:1287–1294

    Article  CAS  Google Scholar 

  • Lee JC, Yu MK, Lee R, Lee YH, Jeon JG, Lee MH, Jhee EC, Yoo ID, Yi HK (2008) Terrein reduces pulpal inflammation in human dental pulp cells. J Endod 34:433–437

    Article  Google Scholar 

  • Liao WY, Shen CN, Lin LH, Yang YL, Han HY, Chen JW, Kuo SC, Wu SH, Liaw CC (2012) Asperjinone, a nor-neolignan, and terrein, a suppressor of ABCG2-expressing breast cancer cells, from thermophilic Aspergillus terreus. J Nat Prod 75:630–635

    Article  CAS  Google Scholar 

  • Lin T, Lu C, Shen Y (2009) Secondary metabolites of Aspergillus sp. F1, a commensal fungal strain of Trewia nudiflora. Nat Prod Res 23:77–85

    Article  CAS  Google Scholar 

  • Magalhães LG, Machado CB, Morais ER, Moreira EB, Soares CS, da Silva SH, da Silva Filho AA, Rodrigues V (2009) In vitro schistosomicidal activity of curcumin against Schistosoma mansoni adult worms. Parasitol Res 104:1197–1201

    Article  Google Scholar 

  • Malmstrøm J, Christophersen C, Barrero AF, Oltra JE, Justicia J, Rosales A (2002) Bioactive metabolites from a marine-derived strain of the fungus Emericella variecolor. J Nat Prod 65:364–367

    Article  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  Google Scholar 

  • Nagia MM, El-Metwally MM, Shaaban M, El-Zalabani SM, Hanna AG (2012) Four butyrolactones and diverse bioactive secondary metabolites from terrestrial Aspergillus flavipes MM2: isolation and structure determination. Org Med Chem Lett 2:01–08

    Article  Google Scholar 

  • Ng LT, Chiang LC, Lin YT, Lin CC (2006) Antiproliferative and apoptotic effects of tetrandine on different human hepatoma cell lines. Am J Chin Med 34:125–135

    Article  CAS  Google Scholar 

  • Nishio K, Ishida T, Arioka H, Kurokawa H, Fukuoka K, Nomoto T, Fukumoto H, Yokote H, Saijo N (1996) Antitumor effects of butyrolactone I, a selective cdc2 kinase inhibitor, on human lung cancer cell lines. Anticancer Res 16:3387–3395

    CAS  Google Scholar 

  • Niu X, Dahse HM, Menzel KD, Lozach O, Walther G, Meijer L, Grabley S, Sattler I (2008) Butyrolactone I derivatives from Aspergillus terreus carrying an unusual sulfate moiety. J Nat Prod 71:689–692

    Article  CAS  Google Scholar 

  • Palomino JC, Martin A, Camacho M, Guerra H, Swings J, Portaels F (2002) Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 46:2720–2722

    Article  CAS  Google Scholar 

  • Park SH, Kim DS, Kim WG, Ryoo IJ, Lee DH, Huh CH, Youn SW, Yoo ID, Park KC (2004) Terrein: a new melanogenesis inhibitor and its mechanism. Cell Mol Life Sci 61:2878–2885

    Article  CAS  Google Scholar 

  • Rahman S, Salehin F, Iqbal A (2011) In vitro antioxidant and anticancer activity of young Zingiber officinale against human breast carcinoma cell lines. BMC Complement Altern Med 11:01–07

    Article  Google Scholar 

  • Raistrick H, Smith G (1935) Studies in the biochemistry of micro-organisms: the metabolic products of Aspergillus terreus Thom. A new mould metabolic product-terrein. Biochem J 29:606–611

    Article  CAS  Google Scholar 

  • Ramos HP, Simão MR, de Souza JM, Magalhães LG, Rodrigues V, Ambrósio SR, Said S (2013) Evaluation of dihydroisocoumarins produced by the endophytic fungus Arthrinium state of Apiospora montagnei against Schistosoma mansoni. Nat Prod Res 27:2240–2243

    Article  CAS  Google Scholar 

  • Rao KV, Sadhukhan AK, Veerender M, Ravikumar V, Mohan EV, Dhanvantri SD, Sitaramkumar M, Babu JM, Vyas K, Reddy GO (2000) Butyrolactones from Aspergillus terreus. Chem Pharm Bull 48:559–562

    Article  CAS  Google Scholar 

  • Rosa LH, Gonçalves VN, Caligiorne RB, Alves TMA, Rabello A, Sales PA, Romanha AJ, Sobral MEG, Rosa CA, ZaniI CL (2010) Leishmanicidal, trypanocidal, and cytotoxic activities of endophytic fungi associated with bioactive plants in Brazil. Braz J Microbiol 41:420–430

    Article  Google Scholar 

  • Rosa LH, Tabanca N, Techen N, Wedge DE, Pan Z, Bernier UR, Becnel JJ, Agramonte NM, Walker LA, Moraes RM (2012) Diversity and biological activities of endophytic fungi associated with micropropagated medicinal plant Echinacea purpurea (L.) Moench. Am J Plant Sci 3:1105–1114

    Article  Google Scholar 

  • Schulz B, Boyle C (2005) The endophytic continuum. Mycol Res 109:661–686

    Article  Google Scholar 

  • Shibata A, Ibaragi S, Mandai H, Tsumura T, Kishimoto K, Okui T, Hassan NM, Shimo T, Omori K, Hu GF, Takashiba S, Suga S, Sasaki A (2016) Synthetic terrein inhibits progression of head and neck cancer by suppressing angiogenin production. Anticancer Res 36:2161–2168

    CAS  Google Scholar 

  • Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370

    Article  CAS  Google Scholar 

  • Suzuki M, Hosaka Y, Matsushima H, Goto T, Kitamura T, Kawabe K (1999) Butyrolactone I induces cyclin B1 and causes G2/M arrest and skipping of mitosis in human prostate cell lines. Cancer Lett 138:121–130

    Article  CAS  Google Scholar 

  • Trabolsy ZBKA, Anouara EH, Zakariaa NSS, Zulkefleeb M, Hasanb MH, Zinb MM, Ahmada R, Sultana S, Webera J-FF (2014) Antioxidant activity, NMR, X-ray, ECD and UV/vis spectra of (+)-terrein: experimental and theoretical approaches. J Mol Struct 1060:102–110

    Article  Google Scholar 

  • Verza M, Arakawa N, Lopes N, Kato M, Pupo M, Said S, Carvalho I (2009) Biotransformation of a tetrahydrofuran lignan by the endophytic fungus Phomopsis sp. J Braz Chem Soc 20:195–200

    Article  CAS  Google Scholar 

  • Wakana D, Hosoe T, Itabashi T, Nozawa K, Kawai K, Okada K, de Campos TGM, Yaguchi T, Fukushima K (2006) Isolation of isoterrein from Neosartorya fisheri. Mycotoxins 56:03–06

    Article  CAS  Google Scholar 

  • Wang Q-X, Li S-F, Zhao F, Dai H-Q, Bao L, Ding R, Gao H, Zhang L-X, Wen H-A, Liu H-W (2011) Chemical constituents from endophytic fungus Fusarium oxysporum. Fitoterapia 82:777–781

    Article  CAS  Google Scholar 

  • Zhang F, Mijiti M, Ding W, Song J, Yin Y, Sun W, Li Z (2015a) (+)-Terrein inhibits human hepatoma Bel-7402 proliferation through cell cycle arrest. Oncol Rep 33:1191–1200

    CAS  Google Scholar 

  • Zhang P, Li X-M, Wang J-N, Li X, Wang B-G (2015b) New butenolide derivatives from the marine-derived fungus Paecilomyces variotii with DPPH radical scavenging activity. Phytochem Lett 11:85–88

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank to the National Council for Scientific and Technological Development (CNPq) (Grant No. 552240/2011-7), Coordination for the Improvement of Higher Education Personnel (CAPES), and National Institute of Science and Technology in Wetlands (INAU) for institutional and financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marcos Antônio Soares.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Silva, I.P., Brissow, E., Kellner Filho, L.C. et al. Bioactive compounds of Aspergillus terreus—F7, an endophytic fungus from Hyptis suaveolens (L.) Poit. World J Microbiol Biotechnol 33, 62 (2017). https://doi.org/10.1007/s11274-017-2228-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11274-017-2228-3

Keywords

Navigation