Anticancer Activities and Mechanisms of Bisdioxopiperazine Compounds Probimane and MST-16

Da-Yong      Lu; Ting-Ren      Lu

doi:10.2174/1871520611009010078

Abstract

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.

Keywords: Bisdioxopiperazine, probimane, MST-16, razoxane, neoplasm metastasis, anticancer pharmacology, anti-neoplastic drugs, antimetastatic drugs, calmodulin, sialic acids, cell-cycle arrest, fibrinogen, cell-movement, lipoperoxidation, drug metabolism, lymphocyterosette-formation