Design And Synthesis Of Hybrid Containing Pyrimidone And Cinnamic Acid And Evaluation Of Their Biological Activity

It is one of the important means and ways for discovery of new drugs to reasonable modification and transformation structural of lead compounds and natural products.Pyrimidone and cinnamic acid are two types of very important active compounds.Pyrimidone and its derivatives with a wide range of physiological and pharmacological activities,play an important role in the field of medicine.Cinnamic acid is a natural active compound,widely found in nature.Cinnamic acid derivatives are widely used in clinical practice due to a wide range of physiological activity.It is most concerning for design and synthesis of hybrids to obtain medicinal molecules with better pharmacological activity.Therfore,we design and synthesize a series of hybrids containing pyrimidone and hydroxycinnamic acid compounds with different substituent groups.Their biological antioxidant activity and structure-activity relationships are researched.Details are as follows:1.A series of 3,4-Dihydropyrimidin-2(1H)-one-cinnamic acid compounds,which have dual-pharmacophore due to the backbone combined by 3,4-dihydropyrimidone and hydroxycinnamic acid compound were synthesized in modest yields via Biginelli multi-component cyclocondensation of ?,?-unsaturated carbonyl compounds,benzaldehyde,and urea or thiourea.The method has the advantages of simple work-up procedure,economy and under environmentally friendly conditions.2.We systematically characterized their antioxidant activity by the2,2-diphenyl-1-picrylhydrazyl free radical(DPPH·)-scavenging,ferric reducing antioxidant power(FRAP)respectively.Our results show that their antioxidant activity depends significantly on substituents of phenyl ring,the reaction mediums and substrates.Specifically,the hydroxyl on the phenyl ring of hydroxycinnamic acid skeleton plays a major role.3.The interaction between bovine serum albumin(BSA)and a series of hybrid compounds were further studied by fluorescence spectroscopy.The results reveal that the binding ability of these compounds and BSA are very good and the different substituents on the phenyl ring effect on binding ability is very small.4.A new pyrimidine thione analog was synthetized by curcumin and thiourea.We systematically characterized their antioxidant activity by the methods of the2,2-diphenyl-1-picrylhydrazyl free radical(DPPH·)-scavenging(hydrogen transfer capability)and ferric reducing antioxidant power(FRAP)(electron donating ability).Finally,themechanism of interaction between the product,curcumin and BSA was studied by fluorescence quenching.The results indicate that the compound shows significant antioxidant effect,and can combine with BSA very well.