Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

Abstract

The synthesis, the antioxidative properties and the lipoxygenase (LOX) and acetylcholinesterase (AChE) inhibition of a number of 4-hydroxy-chalcones diversely substituted as well as of a series of bis-chalcones ether derivatives are reported. The chalcones derivatives were readily produced using a Claisen–Schmidt condensation in a ultra sound bath in good yields. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity is experimentally determined by reversed-phase thin-layer chromatography method. Most of them are potent in vitro inhibitors of lipid peroxidation and of LOX. Compounds b2 and b3 were found to be the most potent LOX and AChE inhibitors among the tested derivatives with a significant anti-lipid peroxidation profile. The results led us to propose these enone derivatives as new multifunctional compounds against Alzheimer's disease. The results are discussed in terms of structural and physicochemical characteristics of the compounds. Moreover, the pharmacokinetic profile of these compounds was investigated using computational methods.

• Acetylcholinesterase inhibitors
• bis-chalcones
• chalcones
• lipoxygenase inhibitors
• multitarget agents

Acknowledgements

We would like to thank Dr A. Leo and Biobyte Corp., 201 West 4th Str., Suite 204, Claremont, CA 91711, USA for free access to the C-QSAR program. We are also grateful to Prof. Gabriele Cruciani (Laboratory of Chemoinformatics and Molecular Modeling, School of Chemistry, University of Perugia, Italy) for kindly providing us the MetaSite and Volsurf programs.

Declaration of interest

The authors report no conflicts of interest.