Acetylcholinesterase (AChE) is an attractive target of drugs for Alzheimer’s disease (AD).
A series of novel synthesized flavonoid derivatives have been reported as potent AChE inhibitors, but
the lack of structure-AChE inhibitory activity relationships hampers the design of specific and selective
flavonoid derivatives. In this study, 3D-quantitative structure activity relationship (3D-QSAR)
models of 90 flavonoid derivatives as AChE inhibitors were established by using CoMFA and CoMSIA
techniques. The results showed that both CoMFA model (q2= 0.651, r2= 0.939, F value = 173.5 and SEE=0.218 ) and
CoMSIA model (q2= 0.680, r2= 0.947, F value = 151.8 and SEE=0.226) demonstrated statistically significant results and
good predictive ability. Furthermore, docking studies were used for better understanding of the binding modes between
flavonoid inhibitors and AChE. In conclusion, the essential information obtained from this study could provide valuable
insight for further modification of highly potent AChE inhibitors.
Keywords: AChE inhibitors, flavonoid derivatives, 3D-QSAR, CoMFA, CoMSIA, molecular docking.
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