Stereochemistry, metabolism, and antitumor activity of 4-hydroperoxyisophosphamide (NSC-227114) and its stereoisomer

Cancer Treat Rep. 1976 Apr;60(4):361-8.

Abstract

An acid-catalyzed isomerization of 4-hydroperoxyisophosphamide, a synthetic compound with potential antitumor activity, produced a new crystalline epimer having an inverted stereochemistry at the phosphorus atom. The stereochemistry of these epimeric hydroperoxides is discussed on the basis of their chemical and nuclear magnetic resonance properties. The epimers show essentially the same metabolic behavior. This behavior is, however, different from that of isophosphamide (IP) which is metabolized in part via pathways ineffective for its activation. The newly isolated epimer shows slightly higher activity against some kinds of experimental tumors than the original hydroperoxide, suggesting that the inverted stereochemistry of the alkylating group at the phosphorus atom is effective in promoting the antitumor activity of the activated species of IP.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Carcinoma, Ehrlich Tumor / drug therapy
  • Cells, Cultured
  • Chemical Phenomena
  • Chemistry
  • Cyclophosphamide / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Female
  • HeLa Cells
  • Ifosfamide / analogs & derivatives*
  • Ifosfamide / therapeutic use
  • Lethal Dose 50
  • Leukemia L1210 / drug therapy
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Peroxides / pharmacology
  • Rats
  • Sarcoma, Yoshida / drug therapy
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Peroxides
  • Cyclophosphamide
  • Ifosfamide