QSAR modeling on binding affinity of diverse estrogenic flavonoids: electronic, topological and spatial functions in quantitative approximation

Phytoestrogens have been explored as promising next generation estrogenic drug candidates with minimum cardiovascular risks. Investigating spatial, electronic and topological properties of the molecules, structure-activity relationships were drawn in an endeavor to find out the basic pharmacophore features of flavonoids for binding with the estrogen receptor. Implementing multi-parameter linear regression analysis, a significant relationship (R2=0.892 and Q2=0.805 for n=19) was established that explained 86.097% variance in binding affinity to the receptor. This study revealed the importance of partial charges at atoms C2′ and C4′ in the phenyl ring C, electrotoplogical state of atom C7 in the phenyl ring A and the molecular orientation and conformational stringency factors. It has been found that substitution by an e− donating group in the phenyl ring at C2′, e− withdrawing groups at C4′ and C7 of the molecule in conjunction with minimal conformational rigidity could be important for estrogenic activity.