3D-QSAR analysis of Tacrine−4-Oxo-4H-chromene Hybrids as Multifunctional Agents for the Treatment of Alzheimer’s disease by CoMFA and CoMSIA

3D QSAR is a powerful tool for explaining the relationships between chemical structure and experimental observations [1]. 3D-QSAR studies have been carried out on a series of (29 compounds) of tacrine− 4-oxo-4H-chromene hybrids. Tacrine – 4 – oxo - 4H - chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h- BuChE), being more potent than the parent inhibitor, tacrine [2]. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. To have a more reliable and flexible model before any data calibration the molecules were spliited to train and test sets. An alignment rule for the compounds was defined using Distill option in SYBYL 1.3. It accomplished by selection of maximum common substructure by using the most active compound. Then according to database methodology will align all molecular stuctures on it. Models were validated using a data set obtained by dividing the data set into a training set and test set using hierarchical clustering, based on the CoMFA fields and biological activities (pIC50). QSAR model had good statistical parameters and yielded q2 = 0.568; r2=0.853. The quality of CoMSIA was lower than that of CoMFA region focusing in terms of q2 and r2 values. The statistical parameters from the models indicate that the data are Well fitted and have high predictive ability.