The metabolism and antitumour activity of the enantiomers of cis- and trans-4-methylcyclophosphamide

Peter B. Farmer, Michael Jarman, Terenzio Facchinetti, Krzysztof Pankiewicz, Wojciech J. Stec

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Abstract

4-Methylcyclophosphamide, an analogue of the antitumour agent cyclophosphamide, exists in cis and trans forms, each of which comprises a pair of optical isomers. The extents of metabolism by rat liver microsomes during 20 min were compared for the four stereoisomers incubated separately, and for the racemic cis and trans-derivatives in admixture, using mass spectrometry and gas chromatography respectively. In comparative antitumour tests against the ADJ/PC6 plasma cell tumour in mice, the racemic cis and trans forms of 4- and 6-methylcyclophosphamide had similar therapeutic indices. The four stereoisomers of 4-methylcyclophosphamine exhibited an approx. two-fold range in therapeutic index so that there was no marked effect on either metabolism or antitumour activity occasioned by change of configuration either at C-4 or at phosphorus.

Original languageEnglish (US)
Pages (from-to)47-57
Number of pages11
JournalChemico-Biological Interactions
Volume18
Issue number1
DOIs
StatePublished - Jul 1977

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