A series of genistein-polyamine conjugates(4a–4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases(Ch Es) inh...A series of genistein-polyamine conjugates(4a–4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases(Ch Es) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase(ACh E) with an IC_(50) value of 2.75 μmol/L, which was better than that of rivastigmine(5.60 μmol/L). Lineweaver–Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site(CAS) and the peripheral anionic site(PAS) of ACh E. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a–4h did not affect Hep G-2 cell viability at the concentration of 10 μmol/L.展开更多
基金the National Natural Science Foundation of China (Nos. 21172053 and 21302041)the China Postdoctoral Science Foundation (No. 2012M521391)+1 种基金the Postdoctoral Science Foundation of Henan Province (No. 2011015)the Foundation of Henan Educational Committee (No. 14A350008)
文摘A series of genistein-polyamine conjugates(4a–4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases(Ch Es) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase(ACh E) with an IC_(50) value of 2.75 μmol/L, which was better than that of rivastigmine(5.60 μmol/L). Lineweaver–Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site(CAS) and the peripheral anionic site(PAS) of ACh E. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a–4h did not affect Hep G-2 cell viability at the concentration of 10 μmol/L.
