Investigations into the Lymphopaenic and lmmunosuppressive Properties of the Antitumour Agent, Mitoclomine

Abstract

The formula of Mitoclomine (W.B. 7007) was suggested by Granger in 1966 (1) as
that of a useful cytotoxic agent, and confirmed in a number of experimental tumours.

It had been shown previously th<!,t the synthetic vitamin K, Synkavit was concentrated
by some tumour systems (2, 3) arid possessed useful radiosensitising properties (4, 5).
Vitamin K5, although not studied to the same extent as Synkavit, was also thought to
share those properties and the molecule lent itself to substitution of the amine radicle
with a N-N-bischlorethyl group.

Previous studies by lVhisson and Connors (6, 7) had demonstrated that in aniline
mustard compounds the group in the para position to a mustard on the benzene ring
could influence the overall toxicity and cytotoxic activity of the compound. A parahydroxy
aniline mustard derivate had increased toxicity and decreased therapeutic
index when compared with aniline mustard itself, but a paramethoxy derivative showed
an increased cytotoxic activity with decreased toxicity. The vitamin K5 molecule was,
therefore, modified further by substituting a methoxy for a hydroxy group. Granger ( 1)
reported that this compound possessed useful cytotoxic activity against various animal
tumour systems. An additional observation was that of a concurrent selective depressant
effect on the blood lymphocyte without reduction of the polymorphonuclear count.