Novel asymmetric 3,5-bis(arylidene)piperidin-4-one derivatives: synthesis, crystal structures and cytotoxicity

3,5-Bis(arylidene)piperidin-4-one derivatives (BAPs) display good antitumour activity because of their double α,β-unsaturated ketone structural characteristics. Reported BAPs have generally been symmetric and asymmetric BAPs have been little documented. Three asymmetric BAPs, namely (5 E )-3-(4- tert -butylbenzylidene)-5-(4-fluorobenzylidene)-1-methylpiperidin-4-one, C 24 H 26 FNO, ( 5 ), (5 E )-3-(4- tert -butylbenzylidene)-5-(3,5-dimethoxybenzylidene)-1-methylpiperidin-4-one, C 26 H 31 NO 3 , ( 6 ), and (5 E )-3-{3-[( E )-(2,3-dihydroxybenzylidene)amino]benzylidene}-5-(2-fluorobenzylidene)-1-methylpiperidin-4-one, C 27 H 23 FN 2 O 3 , ( 12 ), were generated by Claisen–Schmidt condensation. They are characterized by NMR and FT–IR spectroscopies, and elemental analysis. Single-crystal structure analysis reveals that the two arylidene rings on both sides of the BAP structures adopt an E stereochemistry of the olefinic double bonds and the compounds are E , E isomers. Molecules of ( 5 ) and ( 12 ) generate one-dimensional chains through intermolecular hydrogen bonds, while compound ( 6 ) generates a two-dimensional network through hydrogen bonds. Preliminary cytotoxicities toward human liver hepatocellular carcinoma cell line (HepG2), human acute mononuclear granulocyte leukaemia (THP-1) and human normal hepatical cell line (LO2) were evaluated.