The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones

This study demonstrated that replacement of the axial protons on the C2 and C6 atoms of various 1-methyl-3,5-bis(benzylidene)-4-piperidones 3 by a dimethylene bridge leading to series 2 lowered cytotoxic potencies. Four compounds 2a and 3a–c emerged as lead molecules based on their toxicity towards different neoplasms and their selective toxicity for malignant rather than normal cells. Some possible reasons for the disparity between the IC50 values in the two series of compounds are presented based on molecular modeling, log P values and respiration in rat liver mitochondria.

The incorporation of a dimethylene bridge between the C2 and C6 atoms of series 3 led to series 2 with reduced cytotoxic potencies. This disparity in cytotoxic potencies was attributed inter alia to differences in topography, log P values and effect on respiration in mitochondria.Figure optionsDownload as PowerPoint slide