EVALUATION OF SOME MANNICH-BASES OF CYCLOALKANONES AND RELATED-COMPOUNDS FOR CYTOTOXIC ACTIVITY

A number of Mannich bases of cycloalkanones and related quaternary amm onium compounds were prepared for cytotoxic evaluation in order to exa mine the theory that sequential release of alkylating agents produces increased bioactivity compared to related compounds containing only 1 potential alkylating site. Many of the compounds had significant activ ity against murine L1210 cells and various human tumours. Some correla tions between structure and activity were noted but the biological dat a did not support the view that potential sequential liberation of cyt otoxic species produced compounds with increased potency. The formatio n of various oximes and oxime benzoates as candidate prodrugs was achi eved but in general these compounds were not cytotoxic at the concentr ations utilized. This observation may be due to the fact that the oxim es were much more stable in deuterated phosphate buffered saline over a period of 48 h at 37-degrees-C than the Mannich bases, as revealed b y H-1-NMR spectroscopy.