SYNTHESIS AND CYTOTOXICITY OF AMINE-BORANE ADDUCTS OF CYCLOHEXYLAMINES AND TOLUIDINES

A series of cyano- and carboxyborane adducts of cyclohexylamines and t oluidines were shown to be cytotoxic towards suspended single cell tum ors. The carboxyborane adducts of cyclohexylamine were more potent tha n the cyanoborane adducts of cyclohexylamine or any of the toluidine d erivatives. A number of the compounds were active at 8 mg/kg/day i.p, in the Ehrlich ascites carcinoma screen in vivo. The mode of action st udy with N-methylcyclohexylaminecyanoborane 10 in L-1210 lymphoid leuk emia cells showed that RNA synthesis was markedly reduced followed by DNA synthesis. Purine de novo synthesis was suppressed at PRPP-amido t ransferase, IMP dehydrogenase, and dihydrofolate reductase enzyme site s. The agent also interfered with DNA template activity causing reduct ion of DNA polymerase alpha, and RNA polymerase I, II and III activiti es. The d[NTP] pools were marginally reduced while DNA viscosity was r educed and DNA fragmentation occurred.