Advertisement

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

  • H. Umezawa
Chapter
  • 71 Downloads
Part of the Developments in Pharmacology book series (DIPH, volume 3)

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.

Keywords

Pulmonary Toxicity Total Synthesis Terminal Amine Ehrlich Carcinoma Antitumor Antibiotic 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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.Google Scholar
  2. 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.Google Scholar
  3. 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.Google Scholar
  4. 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.Google Scholar
  5. 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.Google Scholar
  6. 6.
    Hurley LH. 1977. Pyrrolo(l,4)benzodiazepine antitumor antibiotic. Compared aspects of anthramycin, tomaymycin and sibilomycin. J. Antibiotics 30, 349–370.Google Scholar
  7. 7.
    Korman S, Tendler MP. 1965. Clinical investigation of cancer chemotherapeutic agents for neoplastic diseases. J. New Drugs 5, 275–285.PubMedGoogle Scholar
  8. 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.Google Scholar
  9. 9.
    Hisamatsu T, Uchida S, Takeuchi T, Ishizuka M, Umezawa H. 1980. Antitumor effect of a new antibiotic, neothramycin. Gann 71, 308–312.PubMedGoogle Scholar
  10. 10.
    Maruyama IN, Suzuki H, Tanaka N. 1978. Mechanism of action of neothramycin. I. The effect on macromolecular syntheses. J. Antibiotics 31, 761–768.Google Scholar
  11. 11.
    Maruyama IN, Tanaka N, Kondo S, Umezawa H. 1979. Mechanism of action of neothramycin. II. Interaction with DNA. J. Antibiotics 32, 928–934.Google Scholar
  12. 12.
    Maruyama IN, Tanaka N, Kondo S, Umezawa H. 1981. Structure of neothramycin-2’-deoxyguanosine adduct. Biochem. Biophys. Res. Commun. 98, 970–976.PubMedCrossRefGoogle Scholar
  13. 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.Google Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.Google Scholar
  17. 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.Google Scholar
  18. 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. 19.
    Umezawa H, Takita T. 1980. The bleomycins: antitumor copper-binding antibiotics. Structure and Bonding 40, 73–99.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.Google Scholar
  22. 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.Google Scholar
  23. 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.Google Scholar
  24. 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.Google Scholar
  25. 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.PubMedGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 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.Google Scholar
  28. 28.
    Povirk LF ,Hogan M, Dattagupta N. 1979. Binding of bleomycin to DNA: Intercalation of the bithiazole rings. Biochemistry 18, 96–101.PubMedCrossRefGoogle Scholar
  29. 29.
    Povirk LF. 1981. Copper (II) bleomycin, iron (III) bleomycin and copper (II) phleomycin: Comparative study of DNA binding. Biochemistry 20, 665–670.PubMedCrossRefGoogle Scholar
  30. 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.Google Scholar
  31. 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.Google Scholar
  32. 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.Google Scholar
  33. 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. 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.Google Scholar
  35. 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. 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. 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. 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. 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.Google Scholar
  40. 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.Google Scholar
  41. 41.
    Oki T, Yoshimoto A, Matsuzawa Y, Takeuchi T, Umezawa H. 1981. New anthracycline antibiotic, 2-hydroxyaclacinomycin A. J. Antibiotics 34, 916–918.Google Scholar
  42. 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.Google Scholar
  43. 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.Google Scholar
  44. 44.
    Umezawa H. 1972. Enzyme Inhibitors of Microbial Origin. Tokyo, University of Tokyo Press.Google Scholar
  45. 45.
    Umezawa H. 1977. Recent advances in bioactive microbial secondary metabolites. Jap. J. Antibiotics 30 (Suppl.), 138–163.Google Scholar
  46. 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. 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. 48.
    Ishizuka M, Iinuma H, Takeuchi T, Umezawa H. 1972. Effect of diketocoriolin B on antibody formation. J. Antibiotic 320–321.Google Scholar
  49. 49.
    Kunimoto T, Hori M, Umezawa H. 1973. Mechanism of action of diketocoriolin B. Biochim. Biophys. Acta 298, 513–525.CrossRefGoogle Scholar
  50. 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.Google Scholar
  51. 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.PubMedGoogle Scholar
  52. 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.Google Scholar
  53. 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.Google Scholar
  54. 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.Google Scholar
  55. 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.Google Scholar
  56. 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.Google Scholar
  57. 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.PubMedCrossRefGoogle Scholar
  58. 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).Google Scholar

Copyright information

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

Authors and Affiliations

  • H. Umezawa

There are no affiliations available

Personalised recommendations