The metabolism and antitumour activity of the enantiomers of cis- and trans-4-methylcyclophosphamide.
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 steroisomers 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-methylcyclophosphamide 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.
D000818:Animals; D000970:Antineoplastic Agents; D002849:Chromatography, Gas; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010954:Plasmacytoma / Q000188:drug therapy; D051381:Rats; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D003520:Cyclophosphamide