After validation ofdocking calculations, the docking was extended to the 33 ligands.
The dockingresults on BuChE receptor were analyzed using Accelrys DSVisualizer v2.0.1 software for this inhibitor to their respective receptor. Thedocking results revealed that all the studied mono and bis-spiropyrrolizinederivatives have two binding sites (binding site 1 and binding site 2). Thepredicted binding conformations of all investigated inhibitors with lowestbinding energy and their alignment are shown in Fig.8.
Interaction modes ofBuChE receptors with the most (8e compound) and lowest (5e compound) activemolecules were investigated that showed in Fig. 9. Compound 8e selected activesite 1 while 5e was observed in active site 2. Docking studies on the mostpotent inhibitor, 8e, showed that the binding pocket includes Ile69, Asp70,Trp82, Gly116, Gly117, Gln119, Thr120, Ser198, Trp231, Pro285, Leu286, Ser287,Val288, Ala328, Phe329, Tyr332, Phe398, Trp430, Tyr440. The results for thelowest potent inhibitor, 5e, showed that the binding pocket comprises ofVal233, Phe227, Asn228, Pro303, Asp304, Tyr396, Cys400, Pro401, Glu404, Trp522,Thr523, Pro527. The hydrogen bond is the interaction between polar hydrogen andelectron density of electronegative elements (such as oxygen and nitrogen).
Hydrogenbonding plays a significant role in determining a molecule’s physiological orbiochemical role. For 8e- BuChE receptor, there is an important hydrogen bond between thecarbonyl oxygen of Pro285 and one amino hydrogen (>C=O…H–N) with an O…H distance2.055 Å (AutoDock Vina). For 5e-BuChE receptor, there was not any hydrogenbond. Fig. 8.
Fig. 9. The AutoDocksoftware is also employed to determine docking energy for the 33 mono andbis-spiropyrrolizine derivatives toward the BuChE receptor. The results arelisted in Table 8. By the investigationof the correlationbetween inhibitory activity values (IC50)and docking energies, it was clear that there isa good correlation. The calculated docking energy and experimental (IC50)was obtained andshown in Fig.