Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheime

来源 :Acta Pharmaceutica Sinica B | 被引量 : 0次 | 上传用户:yeshen_001
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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. 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. Lineweaver-Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site (ACh E) with an IC 50 value of 2.75 μmol / L, which was better than that of rivastigmine (5.60 μmol / L) (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.
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