不对称1,5-二芳基-1,4-戊二烯-3-酮类化合物的合成及生物活性研究-synthesis and biological activity of asymmetric 1,5 - diaryl - 1,4 - pentadiene - 3 - one compounds.docxVIP

AbstractHepta-2,5-dien-4-one analogues have similar structural characteristics as curcumin and are associated with a wide range of biological activities such as antifungal, anti-cancer, anti-oxidation, anti-inflammatory and so on. These compounds are of considerable importance for the development of novel structures as components of potential drugs. In addition, phenolic ether and carbonate compounds have received extensive attention because of their high efficiency and low toxicity.In order to find suitable curcumin derivatives with high bioactivity, we designed and synthesized three series of new compounds by invoking the principle of obtaining bioactive substructures utilizing the concept of bioisoteric relationships. Thus fourteen asymmetric 1,5-diaryl(substituted)penta-1,4-dien-3-ones(IA), three containing phenol ether structure asymmetric 1,5-diaryl(substituted)penta-1,4-dien-3-ones(IB) and three ethyl phenyl carbonateswere synthesized. Structures of all compounds were identified by 1H NMR, 13C NMR, IR and elemental analysis.Preliminary evaluation of the antifungal activities showed that most of the compounds possess certain antifungal activity on three phytopathogenic fungi. At 50 μg/mL, compound IIIIAAAA3333, IA9, IA11 and IA14 showed inhibition against G. zeae at 40.8% , 41.8%, 43.6% and 51.6% respectively, which is parallel to Hymexozole (61.2%). Compound IIIIAAAA3333, IIIIAAAand IIIIAAAexhibited inhibition against F. oxysporum at 32.5%, 50.3% and 32.9% respectively, which is parallel to Hymexozole (60.2%) and inhibition against C. mandshurica at 33.2%, 40.0% and 34.2% respectively, which is parallel to Hymexozole(57.3%).Preliminary evaluation of the antitumor activities showed that compound IA3, IA4, IA6, IA7, IA10 and IA14 possess certain antitumor activities against PC3 cells in vitro. At 10 μmol/L, compound IA3, IA4, IA6, IA7, IA10 and IA14 showed inhibition against PC3 cells at 83.7%, 87.2%, 87.8%, 83.9%, 88.5% and 82