Synthesis and biological properties of side-chain-modified bleomycins

J Med Chem. 1987 Jan;30(1):20-4. doi: 10.1021/jm00384a003.

Abstract

New side-chain-modified bleomycins (BLMs) 3a-k have been synthesized by the reaction of demethyl BLM A2 with alpha-bromoacetamides (2a-k). The structures of these BLM analogues have been established by comparison of their NMR spectra with the corresponding spectra of model thiazole derivatives. Mass spectra (FAB) of the modified BLMs are not informative, since the fragmentation patterns exhibit a loss of the modified chain moiety, presumably in the matrix. The purity of the compounds is attested by TLC and HPLC analyses. Biological evaluation of 3a-k in in vitro (survival of B16 melanoma cells) shows that the compounds are almost as effective as bleomycin. Examination of the effects of 3c, 3e, and 3f on lungs of male mice indicates that the analogues do not exhibit lower pulmonary toxicity than bleomycin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / chemical synthesis*
  • Bleomycin / therapeutic use
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Melanoma, Experimental / drug therapy
  • Mice
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship

Substances

  • Indicators and Reagents
  • Bleomycin