Design,Synthesis And Anticancer Activity Of Monocarbonyl Curcumin Analogs

Curcumin andβ-ionone are common natural active ingredients in fruits and vegetables,they have significant anti-cancer activities.However,unstablity of curcumin and the low water solubility ofβ-ionone limits their development as anticancer drugs.Therefore,we designed and synthesized some monocarbonyl curcumin analogues based on enhancing the stability.The pharmacological activities of these compounds in vitro were tested by cell biology methods.Reactive oxygen species（ROS）are by-products of normal oxygen metabolism and plays an important role in cell signal transduction and homeostasis maintenance.When stimulated by exogenous substances,the level of ROS in cancer cells increases,and the excessive accumulation of ROS can seriously damage the cell structure and eventually lead to apoptosis.Therefore,ROS production can be increased and cancer cells can be killed by introducing exogenous substances.We designed and synthesized two series of monocarbonyl curcumin analogues and evaluated their anticancer activity.Then,we explored the anticancer mechanism of curcumin analogue:Six mono-carbonyl curcumin analogs with the ortho-hydroxy group（1a¹f）were synthesized.The structures of synthesized compounds were confirmed by ¹H and ¹³C NMR spectral data and evaluated for their anti-cancer activities by the MTT assay.Among the compounds studied,1-acryloyl-3,5-Bis（2-hydroxy-benzylidene）-4-piperidone（1f）was more potent compound,with about 10-fold cytotoxicity relative to curcumin in A549 cells.Compound 1f could induce the generation of reactive oxygen species（ROS）,then disrupt the intracellular redox balance,induce lipid peroxidation,cause the collapse of the mitochondrial membrane potential and ultimately lead to apoptosis.Nineteen monocarbonyl analogues ofβ-ionone（2a²s）were synthesized.The structures of synthesized compounds were confirmed by ¹H and ¹³C NMR spectral data and evaluated for their anti-cancer activities by the MTT assay.Cytotoxic activity assays showed that the anticancer activity of the compounds was superior toβ-ionone and was affected by"positional effects"and"electronic effects."...