Studies on the effects of the antitumor agent camptothecin and derivatives on DNA. Camptothecin potentiated cleavage of DNA by bleomycin in vitro

Chemico-biological Interactions
J W LownJ A Plambeck

Abstract

Addition of sodium camptothecin (2a, Fig. 1) in comparable low concentrations to the glycopeptide antitumor antibiotic bleomycin (BLM) leads to enhanced rates of single-strand scission of PM2-covalently closed circular DNA, whereas sodium camptothecin alone has no effect. A similar enhancement of DNA scission by sodium camptothecin is produced with the 1 : 1 bleomycin-iron complex alone or in conjunction with NADPH as an additional reductant. The interpretation that camptothecin may substitute for the reducing requirement of the antibiotic is supported by its oxidation at 37 degrees C by the 1 : 1 bleomycin iron complex, by iron salts or more efficiently by hydrogen peroxide to the known hemiacetal (3, Fig. 1). Electrochemical studies of 2a, its analogues and selected model compounds established that the alpha-pyridone ring D is most susceptible to a one-electron reduction at a reversible potential of -0.95 +/- 0.01 V. The reduced camptothecin is a transient species readily capable of donating an electron. This process may by compatible with a coupled reduction of the sequestered Fe(III) in the glycopeptide antibiotic necessary for the expression of antibiotic and antitumor properties. The results may provide a mechanistic rati...Continue Reading

References

Aug 22, 1977·Biochemical and Biophysical Research Communications·J W Lown, S K Sim
Jul 11, 1978·Biochemistry·E A SausvilleS B Horwitz
Jan 9, 1979·Biochemistry·L F PovirkN Dattagupta
Jun 6, 1977·Biochemical and Biophysical Research Communications·J W LownR Y Chang
Mar 1, 1976·Canadian Journal of Biochemistry·R ConeA R Morgan
Feb 1, 1972·Canadian Journal of Biochemistry·A R Morgan, V Paetkau
Nov 5, 1971·Biochemical and Biophysical Research Communications·M S Horwitz, S B Horwitz
Aug 26, 1971·Biochimica Et Biophysica Acta·D Kessel

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