Planta Med 2002; 68(12): 1113-1117
DOI: 10.1055/s-2002-36340
Original Paper
Physiology
© Georg Thieme Verlag Stuttgart · New York

Biotransformation of 2α,5α,10β,14β-Tetraacetoxy-4(20),11-taxadiene by Cell Suspension Cultures of Catharanthus roseus

Jungui Dai1 , Yajun Cui1 , Weihua Zhu2 , Hongzhu Guo1 , Min Ye1 , Qiu Hu2 , Dayong Zhang2 , Junhua Zheng1 , Dean Guo1
  • 1The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, P.R.China
  • 2Institute of Materia Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, P.R.China
Weitere Informationen

Publikationsverlauf

Received: March 24, 2002

Accepted: July 13, 2002

Publikationsdatum:
20. Dezember 2002 (online)

Abstract

Catharanthus roseus cell suspension cultures were employed for the biotransformation of 2α,5α,10β,14β-tetraacetoxy-4(20),11-taxadiene (1), and four metabolites were obtained. Based on their physical and chemical data, the structures of the four metabolites were respectively elucidated as 10β-hydroxy-2α,5α,14β-triacetoxy-4(20),11-taxadiene (2), 5α-hydroxy-2α,10β, 14β-triacetoxy-4(20),11-taxadiene (3), 6α,10β-dihydroxy-2α,5α,14β-triacetoxy-4(20),11-taxadiene (4), and 6α,9α,10β-trihydroxy-2α,5α,14β-triacetoxy-4(20),11-taxadiene (5), among which 3 and 5 were characterized as new taxoids. The effects of the stages of substrate addition on the biotransformation were also investigated. The results revealed that the biotransformation rate for 1 reached 85.3 % and the yield of 2 70 % when 1 was administered during the mid-linear phase (9 - 12th day) of the cell growth cycle. On the other hand, the yield for 4 reached the highest level of 11.8 % when 1 was added in the early linear phase (6th day).

References

  • 1 Suga T, Hirata T. Biotransformation of exogenous substrates by plant cell cultures.  Phytochemistry. 1990;  29 2393-406 (and references cited therein)
  • 2 Cheng K, Chen W, Zhu W, Fang Q. Manufacture of taxane analog by culture of Taxus plants. PCT Int. Appl. WO9406, 740 (Cl. C07C35/37), 31 Mar 1994, JP Appl. 92/249, 047, 18 Sep 1992
  • 3 Wu Y, Zhu W, Lu J, Hu Q, Li X. Selection and culture of high-yield sinenxans cell lines of Taxus spp. distributed in China.  Chinese Pharmaceutical Journal. 1998;  33 15-8
  • 4 Hosoyama H, Shigemori H, Tomida A, Tsuruo T, Kobayashi J. Modulation of multidrug resistance in tumor cells by taxinine derivatives.  Bioorganic & Medicinal Chemistry Letters. 1999;  9 389-92
  • 5 Sako M, Suzuki H, Yamamoto N, Hirota K. Highly increased cellular accumulation of vincristine, a useful hydrophobic antitumor-drug, in multidrug-resistant solid cancer cells induced by a simply reduced taxinine.  Bioorganic & Medicinal Chemistry Letters. 1999;  9 3403-6
  • 6 Morihira K, Nishimori T, Kusama H, Horiguchi Y, Kuwajima I, Tsuruo T. Synthesis and evaluation of artificial taxoids with antitumor and multi-drug resistance reversing activities.  Bioorganic & Medicinal Chemistry Letters. 1998;  89 2977-81
  • 7 Kosugi K, Sakai J, Zhang S, Watanabe Y, Sasaki H, Suzuki T, Hagiwara H, Hirata N, Hiose K, Ando M, Tomida A, Tsuruo T. Neutral taxoids from Taxus cuspidata as modulators of multidrug-resistant tumor cells.  Phytochemistry. 2000;  54 839-43
  • 8 Dai J, Guo H, Lu D, Zhu W, Zhang D, Zheng J, Guo D. Biotransformation of 2α,5α,10β,14β-tetracetoxy-4(20),11-taxadiene by Ginkgo cell suspension cultures.  Tetrahedron Lett. 2001;  42 4677-9
  • 9 Murashige T, Skoog F. A revised medium for rapid growth and bioassay with tobacco tissue cultures.  Physiology Plant. 1962;  15 473-9
  • 10 Hu S, Tian X, Zhu W, Fang Q. Microbial transformation of taxoids: Selective deacetylation and hydroxylation of 2α,5α,10β,14β-tetracetoxy-4(20),11-taxadiene by the fungus Cunninghamella elegans .  Tetrahedron. 1996;  26 8739-46

Dean Guo, PhD

The State Key Laboratory of Natural and Biomimetic Drugs

School of Pharmaceutical Sciences, Peking University

Xueyuan Road 38

Beijing 100083

P.R.China

eMail: gda@ bjmu.edu.cn

Telefon: +86-10-62091516

Fax: +86-10-62092700

    >