**3.3 Protein-ligand interactions**

Structurally, each of the studied ligand contained the basic flavone skeleton linked by a three-carbon chain forming a closed pyran ring. Considering hydrogen bond interactions of the studied molecules with active amino acids of the estrogen receptor, from the results, the 7-OH of gelagin (**Figure 3** (**a** & **a1**)) formed one hydrogen bond with Glycin 521 at a distance of 1.89 Ǻ and a π-cation interactions with phenylalnine 404 and histidine 524. The 31 - OH and 41 - OH groups of myricetin each established 1H bond with glutamic acid 353 residue at distances of 1.59 Ǻ and 1.74 Ǻ respectively. A firm interaction was also observed with Arginine 394 by the 41 - OH of myricetin at distances of 1.97 Ǻ and 2.26 Ǻ. The 8- OH of myricetin also established 1H bond with histidine 524 and glycin 521 at 1.90 Ǻ. There was also a π-interaction of this ligand with phenylalanine 404 and histidine 524 (**Figure 3** (**b**  & **b1**)). In **Figure 3** (**c** & **c1**) 1H bond each was established between the 8- OH of

**Figure 4.**

*3D and 2D molecular interaction of pinostrobin (d, d1), pinocembrin (e, e1) and with crucial amino acids at the ligand binding domain of hER*α*.*

*Small Molecules Inhibit Extranuclear Signaling by Estrogen: A Promising Strategy to Halt Breast… DOI: http://dx.doi.org/10.5772/intechopen.94052*

pinobankskin and Glycine 521 and Methionine 388 at distances of 1.78 Ǻ and 1.89 Ǻ respectively. A pi-pi interaction was also observed between the ligand and phenyalanine 404 as well as histidine 524. A pi-pi interaction was formed between pinostrobin and phenyalanine 404 of the hERα while its 8- OH group formed one hydrogen bond with glycine 521 at 1.78Ǻ (**Figure 4** (**d** & **d1**)). Pinocembrin (**Figure 4** (**e** & **e1**)) established a pi-cation interaction with phenylalanine 404 and histidine 524 while its 5-OH group formed 1H bond with leucine 387 at 1.89 Ǻ. A strong interaction was observed between its 8- OH group and glutamate 353 at 1.57 Ǻ. Tamoxifen, on the other hand, established 1H bond with Arginine 394 at 2.34 Ǻ and a pi-cation interaction with phenylalanine 404 and histidine while estradiol, the native ligand had 1H bond each with glutamate 353 and histidine 524 at distances of 1.80Ǻ and 2.04Ǻ respectively (**Figure 5** (**f** and **g**)). A pi-pi interaction was also observed with histidine 524 and phenylalanine 404.
