Cytotoxic 2,6-bis(arylidene)cyclohexanones and related compounds

A number of 2-arylidenecyclohexanones 1, 2,6-bis(arylidene)cyclohexanones 2 and related Mannich bases 3-5 were prepared. Various torsion angles as wel l as atomic charges on olefinic carbon atoms were determined by molecular m odelling on all compounds. These molecules showed cytotoxicity towards muri ne P388 and L1210 cells as well as to human Molt 4/C8 and CEM T-lymphocytes . The average cytotoxicity of the dienones 2 was more than three times grea ter than was found with the monoarylidene analogues 1, and, in general, wer e slightly more cytotoxic than the Mannich bases 3-5. A number of the compo unds displayed potency towards a panel of human tumour cell lines and most of the representative compounds in series 2-5 were selectively toxic to col on cancers and leukaemic cells. (C) 2000 Editions scientifiques et medicale s Elsevier SAS.