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 (5E)-3-(4-tert-butylbenzylidene)-5-(4-fluorobenzylidene)-1-methylpiperidin-4-one, C24 H26 FNO, (5), (5E)-3-(4-tert-butylbenzylidene)-5-(3,5-dimethoxybenzylidene)-1-methylpiperidin-4-one, C26 H31 NO3 , (6), and (5E)-3-{3-[(E)-(2,3-dihydroxybenzylidene)amino]benzylidene}-5-(2-fluorobenzylidene)-1-methylpiperidin-4-one, C27 H23 FN2 O3 , (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.