Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter January 11, 2019

Diverse polyketides and alkaloids from Penicillium sp. KHMM: structural elucidation, biological and molecular docking studies

  • Abdelaaty Hamed , Mohamed Ismail , Mohammad M. El-Metwally , Marcel Frese , Tarek M.A. Ibrahim , Atef F. El-Haddad , Norbert Sewald and Mohamed Shaaban ORCID logo EMAIL logo

Abstract

As a continuation of our earlier research concerning the investigation of microbial bioactive secondary metabolites from the terrestrial Penicillium sp.KH Link 1809 isolate KHMM, the fungus was re-cultivated on a large scale to explore its bioactive compounds intensively. Fifteen compounds, including seven alkaloids (1–7), one sesquiterpene (8), an acetylenic system (9), two sterols, and sphengolipid, were identified. Their structures were established on the bases of extensive one- and two-dimensional nuclear magnetic resonance and mass measurements, and by comparison with literature data. The antimicrobial activity of the fungal extract and the corresponding compounds were studied using a panel of pathogenic microorganisms, and their in vitro cytotoxicity against the human cervix carcinoma cell line (KB-3-1) was reported as well. The molecular docking of the isolated compounds showed promising affinities for the alkaloidal compounds 46 towards α, β tubulins.

Acknowledgements

The authors are thankful to the NMR and MS Departments of Bielefeld University for the spectral measurements. We thank Carmela Michalek for the biological activity testing and Marco Wißbrock and Anke Nieß for the technical assistance they extended. This work was financed by the German Academic Exchange Service (DAAD) with funds from the German Federal Foreign Office in the frame of the Research Training Network “Novel Cytotoxic Drugs from Extremophilic Actinomycetes” (Project ID 57166072).

References

1. Blunt JW, Copp BR, Munro MH, Northcote PT, Prinsep MR. Marine natural products. Nat Prod Rep 2003;20:1–48.10.1039/b207130bSearch in Google Scholar PubMed

2. Laatsch H. AntiBase 2017, a data base for rapid structural determination of microbial natural products, and annual updates. Weinheim Germany: Wiley-VCH, 2017.Search in Google Scholar

3. Larsen TO, Smedsgaard J, Nielsen KF, Hansen ME, Frisvad JC. Phenotypic taxonomy and metabolite profiling in microbial drug discovery. Nat Prod Rep 2005;22:672–95.10.1039/b404943hSearch in Google Scholar PubMed

4. Butler MS. The role of natural product chemistry in drug discovery. J Nat Prod 2004;67:2141–53.10.1021/np040106ySearch in Google Scholar PubMed

5. Rasmussen TB, Skinderso ME, Bjarnsholt T, Phipps RK, Christensen KB, Andersen JB, et al. Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 2005;151:1325–40.10.1099/mic.0.27715-0Search in Google Scholar PubMed

6. Li JY, Strobel GA. Jesterone and hydroxy-jesterone antioomycete cyclohexenenone epoxides from the endophytic fungus: Pestalotiopsis jesteri. Phytochemistry 2001;57:261–5.10.1016/S0031-9422(01)00021-8Search in Google Scholar PubMed

7. Brady SF, Clardy J. CR377, a new pentaketide antifungal agentisolated from an endophytic fungus. J Nat Prod 2000;63:1447–8.10.1021/np990568pSearch in Google Scholar PubMed

8. Singh SB, Zink DL, Guan Z, Collado J, Pelaez F, Felock PJ, et al. Isolation, structure and HIV-1 integrase inhibitory activity of xanthoviridicatin E and F two novel fungal metabolites produced by Penicillium chrysogenum. Helv Chim Acta 2003;86:3380–5.10.1002/hlca.200390281Search in Google Scholar

9. Zhang HW, Song YC, Tan RX. Biology and chemistry of endophytes. Nat Prod Rep 2006;23:753–71.10.1039/b609472bSearch in Google Scholar PubMed

10. Song YC, Li H, Ye YH, Shan CY, Yang YM, Tan RX. Endophytic naphthopyrone metabolites are co-inhibitors of xanthine oxidase, SW1116cell and some microbial growths. FEMS Microbiol Lett 2004;241:67–72.10.1016/j.femsle.2004.10.005Search in Google Scholar PubMed

11. Bugni TS, Ireland CM. Marine-derived fungi: a chemically and biologically diverse group of microorganisms. Nat Prod Rep 2004;21:143–63.10.1039/b301926hSearch in Google Scholar PubMed

12. Grovel O, Kerzaon I, Vansteelandt M, Petit KE, Biard JF, Pouchus YF. Marine-derived Penicillium sp.: fungal diversity as a promising source of bioactive compounds. Planta Med 2008;74:SL99.10.1055/s-0028-1083979Search in Google Scholar

13. Frisvad JC. Taxonomy, chemodiversity, and chemoconsistency of Aspergillus, Penicillium, and Talaromyces species. Front Microbiol 2014;5:773.10.3389/fmicb.2014.00773Search in Google Scholar PubMed

14. Strobel G, Daisy B. Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 2003;67:491–502.10.1128/MMBR.67.4.491-502.2003Search in Google Scholar PubMed

15. Hassan AE. Novel natural products from endophytic fungi of Egyptian medicinal plants- chemical and biological characterization. Dissertation, Germany: University of Düsseldorf, 2007.Search in Google Scholar

16. Shaaban M, Sohsah GE, El-Metwally MM, Elfedawy MG, Abdel-Mogib M. Bioactive compounds produced by strain of Penicillium sp. IJSEA 2016;5:2319–7560.10.7753/IJSEA0506.1007Search in Google Scholar

17. Hadfield JA, Ducki S, Hirst N, McGown AT. Tubulin and microtubules as targets for anticancer drugs. Prog Cell Cycle Res 2003;5:309–25.Search in Google Scholar PubMed

18. Mohammed YS, Luckner M. The structure of cyclopenin and cyclopenol, metabolic products from p. cyclopium westling and p. viridicatum westling. Tetrahedron Lett 1963;4:1953–8.10.1016/S0040-4039(01)90948-7Search in Google Scholar

19. Wei MY, Yang RY, Shao CL, Wang CY, Deng DS, She ZG, et al. Isolation, structure elucidation, crystal structure, and biological activity of a marine natural alkaloid, viridicatol. Chem Nat Compd 2011;47:322–5.10.1007/s10600-011-9922-4Search in Google Scholar

20. Ciegler A, Kadis S, Ajl SJ. Microbial toxins: a comprehensive treatise; fungal toxins. Metabolites of Penicillium viridicatum and closely related species. New York: Copyright by Academic press, INC 111 Fifth Avenue, 10003, Vol. VI, 1971:509.Search in Google Scholar

21. Luckner M, Mothes K. On the biosynthesis of 2,3-dihydroxy-4-phenyl-quinoline (viridicatin). Tetrahedron Lett 1962;3:1035.10.1016/S0040-4039(00)70953-1Search in Google Scholar

22. Austin DJ, Myers MB. 3-O-methylviridicatin, a new metabolite from Penicillium puberulum. J Chem Soc 1964;1:1197–8.Search in Google Scholar

23. Zhang C, Ding S, Shi W, Cao F, Zhu H, Wen M. A new quinolinone from freshwater lake-derived fungus Myrothecium verrucaria. Nat Prod Res 2017;31:99–103.10.1080/14786419.2016.1212030Search in Google Scholar PubMed

24. Bu Y, Yamazaki H, Takahashi O, Kirikoshi R, Ukai K, Namikoshi M. Penicyrones A and B, an epimeric pair of α-pyrone-type polyketides produced by the marine-derived Penicillium sp. J Antibiot 2016;69:57–61.10.1038/ja.2015.82Search in Google Scholar PubMed

25. Xin Z, Fang Y, Du L, Zhu T, Duan L, Chen J, et al. Aurantiomides A-C, quinazoline alkaloids from the sponge-derived fungus Penicillium aurantiogriseum SP0-19. J Nat Prod 2007;70:853–5.10.1021/np060516hSearch in Google Scholar PubMed

26. Tsukamoto S, Miura S, Yamashita Y, Ohta T. Aspermytin A: a new neurotrophic polyketide isolated from a marine-derived fungus of the genus Aspergillus. Bioorg Med Chem Lett 2004;14:417–20.10.1016/j.bmcl.2003.10.053Search in Google Scholar PubMed

27. Yang J, Qi X, Li W, Shao G, Yao X, Kitanaka S. WA, a new antifungal antibiotic from a soil fungus strain 38. Chin Chem Lett 1998;9:539–40.Search in Google Scholar

28. Li Q, Yang X, Yang Y, Zhao L, Chen G, Li X, et al. Acyclic isoprenoids of Endophytic Aspergillus sp. Y-12 from Panax notoginseng. Lett Org Chem 2017;14:14–7.10.2174/1570178614666161128144710Search in Google Scholar

29. Shaaban M, Nasr H, Hassan AZ, Asker MS. Bioactive secondary metabolites from endophytic Aspergillus fumigatus: structural elucidation and bioactivity studies. Rev Latinoamer Quím 2013;41:50–60.Search in Google Scholar

30. Hamed A, Abdel-Razek AS, Frese M, Wibberg D, El-Haddad AF, Ibrahim TM, et al. New oxaphenalene derivative from marine-derived Streptomyces griseorubens sp. ASMR4. Z Naturforsch 2017;72:53–62.10.1515/znb-2016-0145Search in Google Scholar

31. Huang X, Chen J, Xu X, Zhang W, Zhao C. A new phenolic compound from Schizonepeta tenuifolia. Chem Nat Compd 2016;52:1005–7.10.1007/s10600-016-1847-5Search in Google Scholar

32. Yang T, Wang W, Wei D, Zhang T, Han B, Yu W. Synthesis of quinazolinones via radical cyclization of α-azidyl benzamides. Org Chem Front 2017;4:421–6.10.1039/C6QO00656FSearch in Google Scholar

33. Das S, Parida R, Sandeep IS, Kar B, Nayak S, Mohanty S. Chemical composition and antioxidant activity of some important betel vine landraces. Biologia 2016;71:128–32.10.1515/biolog-2016-0030Search in Google Scholar

34. Ma Y, Qiao K, Kong Y, Li M, Guo L, Miao Z, et al. A new isoquinolone alkaloid from an endophytic fungus R22 of Nerium indicum. Nat Prod Res 2017;31:951–8.10.1080/14786419.2016.1258556Search in Google Scholar PubMed

35. Zhang Y, Mu J, Essmann F, Feng Y, Kramer M, Bao H, et al. A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus Penicillium crustosum AP2T1. Nat Prod Res 2017;31:985–9.10.1080/14786419.2015.1045906Search in Google Scholar PubMed

36. Cutler HG, Crumley FG, Cox RH, Wells JM, Cole RJ. The biological properties of cyclopenin and cyclopenol. Plant Cell Physiol 1984;25:257–63.Search in Google Scholar

37. Cutler SJ, Cutler HG, Hamdy MK. Synthesis of cyclopenin and cyclopenol intermediates: study of analogue structures and biological activities. J Plant Growth Regul 2000;27:33–41.Search in Google Scholar

38. Yang J, Qi X, Li W, Shao G, Yao X, Kitanaka S. WA, a new antifungal antibiotic from a soil fungus strain 38. Chin Chem Lett 1998;9:539–40.Search in Google Scholar

39. Akiyama S-I, Fojo A, Hanover JA, Pastan I, Gottesman MM. Isolation and genetic characterization of human KB cell lines resistant to multiple drugs. Somat Cell Mol Genet 1985;11:117–26.10.1007/BF01534700Search in Google Scholar PubMed

40. Oiso S, Takayama Y, Nakazaki R, Matsunaga N, Motooka C, Yamamura A, et al. Factors involved in the cisplatin resistance of KCP-4 human epidermoid carcinoma cells. Oncol. Rep. 2014;31:719–26.10.3892/or.2013.2896Search in Google Scholar

41. Bauer AW, Kirby WM, Sherris JC, Truck M. Antibiotic susceptibility testing by a standardized single disk method. Am J ClinPathol 1966;45:493–6.10.1093/ajcp/45.4_ts.493Search in Google Scholar

42. Awantu AF, Lenta BN, Bogner T, Fongang YF, Ngouela S, Wansi JD, et al. Dialiumoside, an Olean-18-ene Triterpenoid from Dialium excelsum. Z Naturforsch 2011;66:624–8.10.1515/znb-2011-0610Search in Google Scholar

43. Sammet B, Bogner T, Nahrwold M, Weiss C, Sewald N. Approaches for the synthesis of functionalized cryptophycins. J Org Chem 2010;75:6953–60.10.1021/jo101563sSearch in Google Scholar PubMed

44. Wolf LK. New software and websites for the chemical enter prise. Chem Eng News 2009;87:48.10.1021/cen-v087n045.p048Search in Google Scholar


Supplementary Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/znc-2018-0145).


Received: 2018-09-23
Revised: 2018-11-19
Accepted: 2018-12-15
Published Online: 2019-01-11
Published in Print: 2019-05-27

©2019 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 3.6.2024 from https://www.degruyter.com/document/doi/10.1515/znc-2018-0145/html
Scroll to top button