Synthesis,Anticancer Activity and Cytotoxicity of Novel Double Schiff-Base Condensed α,β-Unsaturated Keto Derivatives

Abstract

Five double Schiff-base condensed α,β-unsaturated keto derivatives, as curcumin analogues, were synthesised in three steps. Cyclohexanone, or N-methyl-4-pyridone, and 3-nitrobenzaldehyde (2 equiv.) were subjected to Claisen-Schmidt condensation under acid conditions to yield tricyclic dinitro compounds which were reduced to the corresponding diamines and then derivatised at their amino groups with 1-aryl(alkyl)-butan-1,3-diones (MeCOCH₂COR). Anticancer activities of the five compounds against four human carcinoma cell lines and their cytotoxicities for LO₂ cell lines were evaluated by the MTT method. All compounds showed moderate anticancer activity and low cytotoxicity. The single N-methyl-4-piperidinone-derived compound that was synthesised displayed the highest anticancer activity toward THP-1 and the lowest cytotoxicity.