Skip to main content
SpringerLink
Log in

Studies on Antitumour Antibiotics, Low Molecular Weight Immuno-Modifiers and Their Analogs and Derivatives

  • Chapter
Structure-Activity Relationships of Anti-Tumour Agents

Part of the book series: Developments in Pharmacology ((DIPH,volume 3))

  • 101 Accesses

Abstract

Antibiotic research has been expanded to low molecular weight inhibitors of enzymes and immuno-modifiers, and continuous progress is being made in the screening, biosynthesis, and understandings of the mechanism of action of antibiotics, and the development of their useful derivatives.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ishizuka M, Takeuchi T, Masuda T, Fukasawa S, Umezawa H. 1981. Enhancement of immune responses and possible inhibition of suppressor cells by aclacinomycin A. J. Antibiotics 34, 331–340.

    CAS  Google Scholar 

  2. Kondo S, Horiuchi Y, Hamada M, Takeuchi T, Umezawa H. 1979. A new antitumor antibiotic, bactobolin produced by Pseudomonas. J. Antibiotics 32, 1069–1071.

    CAS  Google Scholar 

  3. Umezawa H, Kondo S, Iinuma H, Kunimoto S, Ikeda Y, Iwasawa H, Ikeda D, Takeuchi T. 1981. Structure of an antitumor antibiotic, spergualin. J. Antibiotics 34, 1622–1624.

    CAS  Google Scholar 

  4. Kondo S, Iwasawa H, Ikeda D, Umeda Y, Ikeda Y, Iinuma H, Umezawa H. 1981. The total synthesis of spergualin, an antitumor antibiotic. J. Antibiotics 34, 1625–1627.

    CAS  Google Scholar 

  5. Takeuchi T, Miyamoto M, Ishizuka M, Naganawa H, Kondo S, Hamada M, Umezawa H. 1976. Neothramycins A and B, new antitumor antibiotics. J. Antibiotics 29, 93–96.

    CAS  Google Scholar 

  6. Hurley LH. 1977. Pyrrolo(l,4)benzodiazepine antitumor antibiotic. Compared aspects of anthramycin, tomaymycin and sibilomycin. J. Antibiotics 30, 349–370.

    CAS  Google Scholar 

  7. Korman S, Tendler MP. 1965. Clinical investigation of cancer chemotherapeutic agents for neoplastic diseases. J. New Drugs 5, 275–285.

    PubMed  CAS  Google Scholar 

  8. Kunimoto S, Masuda T, Kanbayashi N, Hamada M, Naganawa H, Miyamoto M, Takeuchi T, Umezawa H. 1980. Mazethramycin, a new member of anthramycin group antibiotics. J. Antibiotics 33, 665–667.

    CAS  Google Scholar 

  9. Hisamatsu T, Uchida S, Takeuchi T, Ishizuka M, Umezawa H. 1980. Antitumor effect of a new antibiotic, neothramycin. Gann 71, 308–312.

    PubMed  CAS  Google Scholar 

  10. Maruyama IN, Suzuki H, Tanaka N. 1978. Mechanism of action of neothramycin. I. The effect on macromolecular syntheses. J. Antibiotics 31, 761–768.

    CAS  Google Scholar 

  11. Maruyama IN, Tanaka N, Kondo S, Umezawa H. 1979. Mechanism of action of neothramycin. II. Interaction with DNA. J. Antibiotics 32, 928–934.

    CAS  Google Scholar 

  12. Maruyama IN, Tanaka N, Kondo S, Umezawa H. 1981. Structure of neothramycin-2’-deoxyguanosine adduct. Biochem. Biophys. Res. Commun. 98, 970–976.

    Article  PubMed  CAS  Google Scholar 

  13. Takita T, Muraoka Y, Nakatani T, Fujii A, Umezawa Y, Naganawa H, Umezawa H. 1978. Chemistry of bleomycin. XIX. Revised structures of bleomycin and phleomycin. J. Antibiotics 31, 801–804.

    CAS  Google Scholar 

  14. Takita T, Umezawa Y, Saito S, Morishima H, Umezawa H, Muraoka Y, Suzuki M, Otsuka M, Kobayashi S, Ohno M. 1981. Total synthesis of deglyco-bleomycin A2. Tetrahedron Letters 22, 671–674.

    Article  CAS  Google Scholar 

  15. Takita T, Umezawa Y, Saito S, Morishima H, Tsuchiya T, Miyake T, Umezawa H, Muraoka Y, Suzuki M, Otsuka M, Ohno M. 1982. Total synthesis of bleomycin A2. Tetrahedron Letters 23, 521–524.

    Article  CAS  Google Scholar 

  16. Umezawa H, Muraoka Y, Fujii A, Naganawa H, Takita T. 1980. Chemistry of bleomycin. XXVII. Cleomycin, a new family of bleomycin-phleomycin group. J. Antibiotics 33, 1079–1082.

    CAS  Google Scholar 

  17. Takita T, Muraoka Y, Fujii A, Itoh H, Maeda K, Umezawa H. 1972. The structure of the sulfur-containing chromophore of phleomycin, and chemical transformation of phleomycin to bleomycin. J. Antibiotics 25, 197–199.

    CAS  Google Scholar 

  18. Umezawa H. 1976. Bleomycin: discovery, chemistry and action. GANN Monograph on Cancer Research, No. 19, pp. 3–36, Tokyo, University of Tokyo Press.

    Google Scholar 

  19. Umezawa H, Takita T. 1980. The bleomycins: antitumor copper-binding antibiotics. Structure and Bonding 40, 73–99.

    Article  CAS  Google Scholar 

  20. Umezawa Y, Morishima H, Saito S, Takita T, Umezawa H, Kobayashi S, Otsuka M, Narita M, Ohno M. 1980. Synthesis of the pyrimidine moiety of bleomycin. J. Am. Chem. Soc. 102, 6630–6631.

    Article  CAS  Google Scholar 

  21. Takita T, Muraoka Y, Nakatani T, Fujii A, Iitaka Y, Umezawa H. 1978. Chemistry of bleomycin. XXI. Metal-complex of bleomycin and its implication for the mechanism of bleomycin action. J. Antibiotics 31, 1073–1077.

    CAS  Google Scholar 

  22. Sugiura Y, Muraoka Y, Fujii A, Takita T, Umezawa H. 1979. Chemistry of bleomycin. XXIV. Deamidobleomycin from view point of metal coordination and oxygen activation. J. Antibiotics 32, 756–758.

    CAS  Google Scholar 

  23. Sugiura Y, Suzuki T, Muraoka Y, Umezawa Y, Takita T, Umezawa H. 1981. Deglycobleomycin-iron complexes: Implications for iron-binding site and role of the sugar portion in bleomycin antibiotics. J. Antibiotics 34, 1232–1236.

    CAS  Google Scholar 

  24. Kuramochi H, Takahashi K, Takita T, Umezawa H. 1981. An active intermediate formed in the reaction of bleomycin-Fe(II) complex with oxygen. J. Antibiotics 34, 576–582.

    CAS  Google Scholar 

  25. Giloni L, Takeshita M, Johnson F, Iden C, Grollman P. 1981. Bleomycin-induced strand-scission of DNA. Mechanism of deoxyribose cleavage. J. Biol. Chem. 256, 8608–8615.

    PubMed  CAS  Google Scholar 

  26. Burger RM, Peisach J, Horwitz SB. 1981. Activated bleomycin. A transient complex of drug, iron and oxygen that degrades DNA. J. Biol. Chem. 256, 11636–11644.

    PubMed  CAS  Google Scholar 

  27. Kasai H, Naganawa H, Takita T, Umezawa H. 1978. Chemistry of bleomycin. XXII. Interaction of bleomycin with nucleic acids, preferential binding to guanine base and electrostatic effect of the terminal amine. J. Antibiotics 31, 1316–1320.

    CAS  Google Scholar 

  28. Povirk LF ,Hogan M, Dattagupta N. 1979. Binding of bleomycin to DNA: Intercalation of the bithiazole rings. Biochemistry 18, 96–101.

    Article  PubMed  CAS  Google Scholar 

  29. Povirk LF. 1981. Copper (II) bleomycin, iron (III) bleomycin and copper (II) phleomycin: Comparative study of DNA binding. Biochemistry 20, 665–670.

    Article  PubMed  CAS  Google Scholar 

  30. Okubo H, Abe Y, Hori M, Asakura H, Umezawa H. 1981. A possible role by bithiazole of bleomycin in causing double-strand scission of DNA. J. Antibiotics 34, 1213–1215.

    CAS  Google Scholar 

  31. Takahashi K, Yoshioka O, Matsuda A, Umezawa H. 1977. Intracellular reduction of the cupric ion of bleomycin copper complex and transfer or the cuprous ion to a cellular protein. J. Antibiotics 30, 861–869.

    CAS  Google Scholar 

  32. Umezawa H, Hori S, Sawa T, Yoshioka T, Takita T, Takeuchi T. 1974. A bleomycin-inactivating enzyme in mouse liver. J. Antibiotics 27, 419–424.

    CAS  Google Scholar 

  33. Umezawa H, Takeuchi T, Hori S, Sawa T, Ishizuka M, Ichikawa T, Kanai T. 1972. Studies on the mechanism of antitumor effect of bleomycin on squamous cell carcinoma. J. Antibiotics 25, 483–484.

    Google Scholar 

  34. Umezawa H, Takahashi Y, Fujii A, Saino T, Shirai T, Takita T. 1973. Preparation of bleomycinic acid: Hydrolysis of bleomycin B2 by a Fusarium acylagmatine amidohydrolase. J. Antibiotics 26, 117–119.

    CAS  Google Scholar 

  35. Takita T, Fukuoka T, Umezawa H. 1983. Chemical cleavage of bleomycin to bleomycinic acid and synthesis of new bleomycins. J. Antibiotics 26, 252–254.

    Google Scholar 

  36. Matsuda A, Yoshioka O, Ebihara K, Ekimoto H, Yamashita T, Umezawa H. 1978. The search for new bleomycins. Bleomycin Current Status and New Developments. pp.299–310. Academic Press.

    Google Scholar 

  37. Matsuda A, Yoshioka 0, Takahashi K, Yamashita T, Ebihara K, Ekimoto H, Abe F, Hashimoto Y, Umezawa H. 1978. Preclinical studies on bleomycin-PEP (NK-631). Bleomycin: Current Status and New Developments, pp.311–332. Academic Press.

    Google Scholar 

  38. Noel JP. 1976. Radioactive metal-bleomycin complex for the diagnosis of cancer. Fundamental and Clinical Studies of Bleomycin (Monograph on Cancer Research No. 19), pp. 301–316. Tokyo, University of Tokyo Press.

    Google Scholar 

  39. Oki T, Matsuzawa Y, Yoshimoto A, Numata K, Kitamura I, Hori S, Takamatsu A, Umezawa H, Ishizuka M, Naganawa H, Suda H, Hamada M, Takeuchi T. 1975. New antitumor antibiotics, aclacinomycins A and B. J. Antibiotics 28, 830–834.

    CAS  Google Scholar 

  40. Dantchev D, Paintrand M, Hayat M, Bourut C, Mathé G. 1979. Low heart and skin toxicity of a tetrahydropyranyl derivative of adriamycin (THP-ADM) as observed by electron and light microscopy. J. Antibiotics 32, 1085–1086.

    CAS  Google Scholar 

  41. Oki T, Yoshimoto A, Matsuzawa Y, Takeuchi T, Umezawa H. 1981. New anthracycline antibiotic, 2-hydroxyaclacinomycin A. J. Antibiotics 34, 916–918.

    CAS  Google Scholar 

  42. Takahashi Y, Naganawa H, Takeuchi T, Umezawa H. 1977. The structures of baumycins Al, A2, 81, B2, Cl and C2. J. Antibiotics 30, 622–624.

    CAS  Google Scholar 

  43. Umezawa H, Takahashi T, Kinoshita M, Naganawa H, Masuda T, Ishizuka M, Tatsuta K, Takeuchi T. 1979. Tetrahydropyranyl derivatives of daunomycin and adriamycin. J. Antibiotics 32, 1082–1084.

    CAS  Google Scholar 

  44. Umezawa H. 1972. Enzyme Inhibitors of Microbial Origin. Tokyo, University of Tokyo Press.

    Google Scholar 

  45. Umezawa H. 1977. Recent advances in bioactive microbial secondary metabolites. Jap. J. Antibiotics 30 (Suppl.), 138–163.

    CAS  Google Scholar 

  46. Umezawa H. 1976. Structures and activities of protease inhibitors of microbial origin. Methods in Enzymology, Vol. 45, pp.678–695. Academic Press.

    Google Scholar 

  47. Umezawa H (ed.). 1981. Small Molecular Immunomodifiers of Microbial Origin — Fundamental and Clinical Studies of Bestatin. Tokyo, Japan Scientific Societies Press; Pergamon Press.

    Google Scholar 

  48. Ishizuka M, Iinuma H, Takeuchi T, Umezawa H. 1972. Effect of diketocoriolin B on antibody formation. J. Antibiotic 320–321.

    Google Scholar 

  49. Kunimoto T, Hori M, Umezawa H. 1973. Mechanism of action of diketocoriolin B. Biochim. Biophys. Acta 298, 513–525.

    Article  CAS  Google Scholar 

  50. Ishizuka M, Takeuchi T, Umezawa H. 1981. Studies on the mechanism of action of diketocoriolin B to enhance antibody formation. J. Antibiotics 34, 95–102.

    CAS  Google Scholar 

  51. Aoyagi T, Suda H, Nagai M, Ogawa K, Suzuki J, Takeuchi T, Umezawa H. 1976. Aminopeptidase activities on the surface of mammalian cells. Biochim. Biophys. Acta 452, 131–143.

    PubMed  CAS  Google Scholar 

  52. Umezawa H, Aoyagi T, Suda H, Hamada M, Takeuchi T. 1976. Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes. J. Antibiotics 29, 97–99.

    CAS  Google Scholar 

  53. Aoyagi T, Tobe H, Kojima F, Hamada M, Takeuchi T, Umezawa H. 1978. Amastatin, an inhibitor of aminopeptidase A, produced by actinomycetes. J. Antibiotics 31, 636–638.

    CAS  Google Scholar 

  54. Aoyagi T, Yamamoto T, Kojiri K, Kojima F, Hamada M, Takeuchi T, Umezawa H. 1978. Forphenicine, an inhibitor of alkaline phosphatase produced by actinomycetes. J. Antibiotics 31, 244–246.

    CAS  Google Scholar 

  55. Umezawa H, Aoyagi T, Hazato T, Uotani K, Kojima F, Hamada M, Takeuchi T. 1978. Esterastin, an inhibitor of esterase, produced by actinomycetes. J. Antibiotics 31, 639–641.

    CAS  Google Scholar 

  56. Umezawa H, Aoyagi T, Uotani K, Hamada M, Takeuchi T, Takahashi S. 1980. Ebelactone, an inhibitor of esterase produced by actinomycetes. J. Antibiotics 33, 1594–1596.

    CAS  Google Scholar 

  57. Muller WEG, Zahn RK, Arendes J, Munsh N, Umezawa H. 1979. Activation of DNA metabolism in T cells by bestatin. Biochem. Pharmacol. 28, 3131–3137.

    Article  PubMed  CAS  Google Scholar 

  58. Noma T, Yata J, Hoshi K, Ishii T. 1981. The effect of bestatin on the lymphocyte functions. J. Jpn. Soc. Cancer Ther. 16, 453–459 (in Japanese).

    CAS  Google Scholar 

Download references

Authors
  1. H. Umezawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Organic Chemistry, Technical University Twente, Enschede, The Netherlands

    D. N. Reinhoudt

  2. MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, UK

    T. A. Connors

  3. Department of Biochemistry, Antonie van Leeuwenhoekziekenhuis, Amsterdam, The Netherlands

    H. M. Pinedo

  4. Koningin Wilhelmina Fonds, The Netherlands Cancer Foundation, Amsterdam, The Netherlands

    K. W. van de Poll

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Martinus Nijhoff Publishers, The Hague, Boston, London

About this chapter

Cite this chapter

Umezawa, H. (1983). Studies on Antitumour Antibiotics, Low Molecular Weight Immuno-Modifiers and Their Analogs and Derivatives. In: Reinhoudt, D.N., Connors, T.A., Pinedo, H.M., van de Poll, K.W. (eds) Structure-Activity Relationships of Anti-Tumour Agents. Developments in Pharmacology, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-6798-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-6798-4_13

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-009-6800-4

  • Online ISBN: 978-94-009-6798-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation