Novel racemic tetrahydrocurcuminoid dihydropyrimidinone analogues as potent acetylcholinesterase inhibitors.
The synthesis of racemic tetrahydrocurcumin- (THC-), tetrahydrodemethoxycurcumin- (THDC-) and tetrahydrobisdemethoxycurcumin- (THBDC-) dihydropyrimidinone (DHPM) analogues was achieved by utilizing the multi-component Biginelli reaction in the presence of copper sulphate as a catalyst. The evaluation of acetylcholinesterase inhibitors for Alzheimer's disease of these compounds showed that they exhibited higher inhibitory activity than their parent analogues. THBDC-DHPM demonstrated the most potent inhibitory activity with an IC50 value of 1.34±0.03μM which was more active than the approved drug galanthamine (IC50=1.45±0.04μM).
T10 T11 T12 T13 T14 T1 T2 T3 T4 T5 T6 T7 T8 T9
CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
THDC tetrahydrobisdemethoxycurcumin tetrahydrocurcuminoid dihydropyrimidinone acetylcholinesterase acetylcholinesterase THBDC dihydropyrimidinone DHPM tetrahydrocurcumin copper sulphate THBDC-DHPM THC tetrahydrodemethoxycurcumin galanthamine