Bisdioxopiperazine compounds, including
ICRF-154 and
razoxane (ICRF-159, Raz), are
anticancer agents developed in the UK specifically targeting
tumor metastases. Further two bisdioxopiperazine derivatives,
probimane (Pro) and
MST-16, have been synthesized at the Shanghai Institute of
Materia Medica, Chinese Academy of Sciences, PR China after 1980. Anticancer activities and mechanisms of Pro and
MST-16 compared with Raz, especially for antiproliferative and antimetastatic effects in vivo and in vitro, have been systematically evaluated in this lab as well as by other authors in China. Novel molecular mechanisms especially relating to the inhibition of
tumor metastasis between
probimane and
razoxane have been especially explored and explained, including pathways of inhibitions against
calmodulin,
sialic acid, lipoperoxidation,
fibrinogen, cell-movement and the cell-cycle arrest. The distributions and excretions of (14)[C]-Pro in mice have been carefully monitored long before for explaining the relationship of pharmacological data between in vitro and in vivo evaluations. Pro is more soluble in water and more strongly active against
tumors than Raz. In our point of view, Pro seems to inherit and retain most of the targets and pathways of other bisdioxopiperazine compounds currently in use and is cytotoxically more potent than the rest of bisdioxopiperazine compounds. Therefore, there is a great potential and significance for further investigations.