Alkaloid Production from Cinchona Cell and Organ Systems

  • E. John Staba
Part of the Basic Life Sciences book series (BLSC, volume 44)

Abstract

Alkaloids from members of the genus Cinchona are important because they are used for antimalarial and antiarrhythmic therapy, and as a beverage bitter. In vitro cultures of species such as Cinchona ledgeriana and C. pubescens are being studied in various laboratories for their production of indole alkaloids, quinoline alkaloids, and anthraquinones, and for use as a micropropagation system. The extent to which cell and organ systems express the quinoline alkaloids quinine and quinidine and how their production is affected by growth regulators, differentiation and morphology, and alkaloid intermediates will be discussed. Examples of alkaloid intermediates to be considered are tryptophan, secologanin, strictosidine (isovincoside), 10-methoxystrictosidine, vincoside, and 10-methoxyvincoside.

Keywords

Malaria Indole Quinoline Indonesia Kinetin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Allan, E.J., and A.H. Scragg (1986) Comparison of the growth of Cinchona ledgeriana Moens suspension cultures is shake flasks and 7 litre air-lift bioreactors. Biotechnol. Lett. 8:635–638.CrossRefGoogle Scholar
  2. 2.
    Anderson, L.A., A.T. Keene, and J.D. Phillipson (1982) Alkaloid production by leaf organ, root organ and cell suspension cultures of Cinchona ledgeriana. Planta Med. 46:25–27.PubMedCrossRefGoogle Scholar
  3. 3.
    Battersby, A.R., and R.J. Parry (1971) Biosynthesis of the cinchona alkaloids. Middle stages of the pathway. J. Chem. Soc. (Sect. D) Chem. Comm. 1:30–31.CrossRefGoogle Scholar
  4. 4.
    Brillanceau, M.H., C. Kan-Fan, S.K. Kan, and H.-P. Husson (1984) Guettardine, a possible biogenetic intermediate in the formation of corynanthe-cinchona alkaloids. Tetrahedron Lett. 25:2767–2770.CrossRefGoogle Scholar
  5. 5.
    Chatterjee, S.K. (1974) Vegetative propagation of high quinine yieldi n g cinchona. Indian J. Hort. 31:174–177.Google Scholar
  6. 6.
    Chatterjee, S.K. (1982) Cultivation of cinchona in Darjeeling Hills, West Bengal. In Cultivation and Utilization of Medicinal Plants, Vol. II, C.K. Atal and B.M. Kapur, eds. CSIR, Jammu-Tawi, India, pp. 222–229.Google Scholar
  7. 7.
    Chung, C.-T.A., and E.J. Staba (1984) Separation and quantitation of cinchona major alkaloids by high-performance liquid chromatography. J. Chromatog. 295:276–281.CrossRefGoogle Scholar
  8. 8.
    Chung, C.-T.A., and E.J. Staba (1987) Effect of precursors on growth and alkaloid production in Cinchona ledgeriana leafshoot organ cultures. Planta Med. (submitted for publication).Google Scholar
  9. 9.
    Chung, C-T.A., and E.J. Staba (1987) Effects of age and growth regulators on growth and alkaloid production in Cinchona ledgeriana leaf-shoot organ cultures. Planta Med. 53:206–210.PubMedCrossRefGoogle Scholar
  10. 10.
    Doraswamy, K., and K.P. Venkatratnam (1982) Chemistry, production and marketing of cinchona alkaloids. In Cultivation and Utilization of Medicinal Plants, Vol II, C.K. Atal and B.M. Kapur, eds. CSIR, Jammu-Tawi, India, pp. 230–243.Google Scholar
  11. 11.
    Dutta, N.L., and C. Quassim (1968) Isolation and characterization of glycosides and alkaloids from heartwood of Cinchona ledgeriana Linn. Indian J. Chem. 6:566–567.Google Scholar
  12. 12.
    Harkes, P.A.A., L. Krijbolder, K.R. Libbenga, R. Wijnsma, T. Nsengiyaremge, and R. Verpoorte (1985) Influence of various media constituents on the growth of Cinchona ledgeriana tissue cultures and the production of alkaloids and anthraquinones therein. Plant Cell Tissue Organ Culture 4:199–214.CrossRefGoogle Scholar
  13. 13.
    Hay, C.A., L.A. Anderson, M.F. Roberts, and J.D. Phillipson (1986) In vitro cultures of cinchona species. Precursor feeding of C. ledgeriana root organ suspension cultures with L-tryptophan. Plant Cell Reports 5:1–4.CrossRefGoogle Scholar
  14. 14.
    Hunter, C.S. (1979) In vitro culture of Cinchona ledgeriana L. J. Hort. Sci. 54:111–114.Google Scholar
  15. 15.
    Hunter, C.S., D.V. McCally, and A.J. Barraclough (1982) Alkaloids produced by cultures of Cinchona ledgeriana L. In Plant Tissue Culture. Proceedings Fifth International Congress of Plant Tissue Cultures, A. Fujiwara, ed. Tokyo, p. 317.Google Scholar
  16. 16.
    Hutchinson, C.R., A.H. Heckendorf, J.L. Straughn, P.E. Daddona, and D.E. Crane (1979) Biosynthesis of camptothecin. 3. Definition of strictosamide as the penultimate biosynthetic precursor. Assisted by 13C and 2H NMR spectroscopy. J. Am. Chem. Soc. 101:3358–3369.CrossRefGoogle Scholar
  17. 17.
    Keene, A.T., L.A. Anderson, and J.D. Phillipson (1983) Investigation of cinchona leaf alkaloids by high-performance liquid chromatography. J. Chromatog. 260:123–128.CrossRefGoogle Scholar
  18. 18.
    Koblitz, H., D. Koblitz, H.-P. Schmauder, and D. Groger (1983) Studies on tissue cultures of the genus Cinchona L. Alkaloid production in cell suspension cultures. Plant Cell Reports 2:122–125.CrossRefGoogle Scholar
  19. 19.
    Koblitz, H., D. Koblitz, H.-P. Schmauder, and D. Groger (1983) Studies on tissue cultures of the genus Cinchona L. In vitro mass propagation through meristem-derived plants. Plant Cell Reports 2:95–97.CrossRefGoogle Scholar
  20. 20.
    Krikorian, A.D., M. Singh, and C.E. Quinn (1981) Aseptic micropropagation of Cinchona: Prospects and problems. In Proceedings of the COSTED Symposium on Tissue Culture of Economically Important Plants, A. Rao, ed. National University of Singapore, pp. 167–174.Google Scholar
  21. 21.
    Leete, E., and J.N. Wemple (1966) Biosynthesis of the cinchona alkaloids. The incorporation of [3-14C]-geraniol into quinine. J. Am. Chem. Soc. 88:4743.CrossRefGoogle Scholar
  22. 22.
    Mellon, F.A., M.J.C. Rhodes, and R.J. Robins (1986) The potential of linked scanning at constant B/E for the rapid identification of cell culture products. Biomed. Env. Mass Spect. 13:155–158.CrossRefGoogle Scholar
  23. 23.
    Mulder-Krieger, Th., R. Verpoorte, and A.B. Svendsen (1982) Tissue culture of Cinchona pubescens: Effects of media modifications on the growth. Planta Med. 44:237–240.PubMedCrossRefGoogle Scholar
  24. 24.
    Mulder-Krieger, Th., R. Verpoorte, M. van der Kreek, and A.B. Svendsen (1984) Identification of alkaloids and anthraquinones in Cinchona pubescens callus cultures: The effect of plant growth regulators and light on the alkaloid content. Planta Med. 50:17–20.PubMedCrossRefGoogle Scholar
  25. 25.
    Mulder-Krieger, Th., R. Verpoorte, Y.P. de Graaf, M. van der Kreek, and A. Baerheim-Svendsen (1982) The effects of plant growth regulators and culture conditions on the growth and the alkaloid content of callus cultures of Cinchona pubescens. Planta Med. 46:15–18.PubMedCrossRefGoogle Scholar
  26. 26.
    Mulder-Krieger, Th., R. Verpoorte, A. de Water, M. van Gessel, B.C.J.A. van Oeveren, and A.B, Svendsen (1982) Identification of the alkaloids and anthraquinones in Cinchona ledgeriana callus cultures. Planta Med. 46:19–24.PubMedCrossRefGoogle Scholar
  27. 27.
    Parr, A.J., R.J. Robins, and J.C. Rhodes (1986) Alkaloid transport in Cinchona spp. cell cultures. Physiol. Veg. 24:419–429.Google Scholar
  28. 28.
    Parr, A.J., R.J. Robins, and M.J.C. Rhodes (1986) Permeabilization of Cinchona ledgeriana cells by dimethyl-sulphoxide. Effects on alkaloid release and long-term membrane integrity. Plant Cell Reports 3:262–265.CrossRefGoogle Scholar
  29. 29.
    Parr, A.J., J.I. Smith, R.J. Robins, and M.J.C. Rhodes (1984) Apparent free space and cell volume estimation: A non-destructive method for assessing the growth and membrane integrity/viability of immobilised plant cells. Plant Cell Reports 3:161–164.CrossRefGoogle Scholar
  30. 30.
    Pfitzner, U., and M.H. Zenk (1982) Immobilization of strictosidine synthase from Catharanthus cell cultures and preparative synthesis of strictosidine. Planta Med. 46:10–14.PubMedCrossRefGoogle Scholar
  31. 31.
    Rao, P.R. (1982) Conversion of quinine to quinidine. In Cultivation and Utilization of Medicinal Plants, Vol II., C.K. Atal and B.M. Kapur, eds. CSIR, Jammu-Tawi, India, pp. 244–250.Google Scholar
  32. 32.
    Rhodes, M.J.C., J. Payne, and R.J. Rhodes (1986) Cell suspension cultures of Cinchona ledgeriana. II. The effect of a range of auxins and cytokinins on the production of quinoline alkaloids. Planta Med. 52:226–229.CrossRefGoogle Scholar
  33. 33.
    Robins, R.J., and M.J.C. Rhodes (1986) The stimulation of anthraquinone production by Cinchona ledgeriana cultures with polymeric adsorbents. Appl. Microbiol. Biotechnol. 24:35–41.CrossRefGoogle Scholar
  34. 34.
    Robins, R.J., J. Payne, and M.J.C. Rhodes (1986) Cell suspension cultures of Cinchona ledgeriana. I. Growth and quinoline alkaloid production. Planta Med. 52:220–225.CrossRefGoogle Scholar
  35. 35.
    Robins, R.J., J. Payne, and M.J.C. Rhodes (1986) The production of anthraquinones by cell suspension cultures of Cinchona ledgeriana. Phytochemistry 25:2327–2334.CrossRefGoogle Scholar
  36. 36.
    Robins, R.J., D.O. Hall, D.-J. Shi, R.J. Turner, and M.J.C. Rhodes (1986) Mucilage acts to adhere cyanobacteria and cultures plant cells to biological and inert surfaces. FEMS Microbiol. Lett. 34:155–160.CrossRefGoogle Scholar
  37. 37.
    Robins, R.J., A.J. Webb, M.J.C. Rhodes, J. Payne, and M.R.A. Morgan (1984) Radioimmunoassay for the quantitative determination of quinine in cultured plant tissues. Planta Med. 50:235–238.PubMedCrossRefGoogle Scholar
  38. 38.
    Sastri, B.N. (1950) The Wealth of India, Vol. II, CSIR, Delhi, India, pp. 163–173.Google Scholar
  39. 39.
    Schmauder, H.-P., D. Groger, H. Koblitz, and D. Koblitz (1985) Shikimate pathway activity in shake and fermenter cultures of Cinchona succirubra. Plant Cell Reports 4:233–236.CrossRefGoogle Scholar
  40. 40.
    Scragg, A.H., P. Morris, and E.J. Allan (1986) The effects of plant growth regulators on growth and alkaloid formation in Cinchona ledgeriana callus culture. J. Plant Physiol. 124:371–377.CrossRefGoogle Scholar
  41. 41.
    Sejourne, M., G. Resplandy, C. Viel, J.C. Chenieux, and M. Rideau (1986) Bioproduction of quinoline alkaloids by Cinchona succirubra strains cultured in vitro. Fitoterapia 57:121–123 (cited in Chem. Abstr. 105:57949g).Google Scholar
  42. 42.
    Staba, E.J., and A.C. Chung (1981) Quinine and quinidine production by cinchona leaf, root and unorganized cultures. Phytochemistry 20:2495–2498.CrossRefGoogle Scholar
  43. 43.
    Van der Heijden, R., I. Hegger, E.J.M. Pennings, R. Verpoorte, R. Wijnsma, and J.A. Duine (1986) An HPLC assay for strictosidine synthase activity. Annual Meeting of the American Society of Pharmacognosy, Ann Arbor, Michigan (presented poster).Google Scholar
  44. 44.
    Verpoorte, R., Th. Mulder-Krieger, J.J. Troost, and A.B. Svendsen (1980) Thin-layer chromatographic separation of cinchona alkaloids. J. Chromatog. 184:79–96.CrossRefGoogle Scholar
  45. 45.
    Verpoorte, R., R. Wijnsma, Th. Mulder-Krieger, P.A.A. Harkes, and A.B. Svendsen (1985) Plant cell and tissue culture of Cinchona species. In Primary and Secondary Metabolism of Plant Cell Cultures, K.-H. Neumann, W. Barz, and E. Reinhard, eds. Springer-Verlag, New York, pp. 196–208.CrossRefGoogle Scholar
  46. 46.
    Whitten, G.H., and D.K. Dougall (1981) Quinine and quinidine accumulation by root, callus and suspension cultures of C. ledgeriana. In Vitro 17:220.Google Scholar
  47. 47.
    Wijnsma, R. (1986) Anthraquinones and alkaloids in cell and tissue cultures of Cinchona species. R. Verpoorte, Copromotor, Doctorate Dissertation, State University of Leiden, Leiden, The Netherlands.Google Scholar
  48. 48.
    Wijnsma, R., J.T.K.A, Go, P.A.A. Harkes, R. Verpoorte, and A.B. Svendsen (1986) Anthraquinones in callus cultures of Cinchona pubescens. Phytochemistry 25:1123–1126.CrossRefGoogle Scholar
  49. 49.
    Wijnsma, R., J.T.K.A. Go, I.N. van Weerden, P.A.A. Harkes, R. Verpoorte, and A.B. Svendsen (1985) Anthraquinones as phytoalexins in cell and tissue cultures of Cinchona species. Plant Cell Reports 4:241–244.CrossRefGoogle Scholar
  50. 50.
    Wijnsma, R., R. Verpoorte, P.A.A. Harkes, T.B. van Vliet, H.J.G. ten Hoopen, and A.B. Svendsen (1986) The influence of initial sucrose and nitrate concentrations on the growth of Cinchona ledgeriana cell suspension cultures and the production of alkaloids and anthraquinones. Plant Cell Tissue Organ Culture 7:21–29.CrossRefGoogle Scholar
  51. 51.
    Wijnsma, R., T.B. van Vliet, P.A.A. Harkes, H.J. van Groningen, R. van der Jeijden, R. Verpoorte, and A.B. Svendsen (1987) A method for the quantitative determination of anthraquinones and alkaloids in cell and tissue cultures of Cinchona sp. Planta Med. 53:78–84.CrossRefGoogle Scholar
  52. 52.
    Wijnsma, R., I.N. van Weerden, R. Verpoorte, P.A.A. Harkes, Ch.B. Lugt, J.J.C. Scheffer, and A.B. Svendsen (1986) Anthraquinones in Cinchona ledgeriana bark infected with Phytophthora cinnamomi. Planta Med. 3:211–212.CrossRefGoogle Scholar
  53. 53.
    Wiryowidagdo, S. (1982) Pembentukan alkaloid dalam kalus kina. Doctorate Dissertation, Institut Teknologi Bandung, Indonesia.Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • E. John Staba
    • 1
  1. 1.Department of Medicinal Chemistry and PharmacognosyUniversity of MinnesotaMinneapolisUSA

Personalised recommendations