Gupta and Mohan

fig. 4: chemical structures of 15 designed compounds

by fragment based de novo design

The synthesis feasibility of 15 prioritized newly generated AChEIs was predicted

by SYLVIA software. All 15 compounds were showing SYLVIA score below

7 suggesting its better predictive synthetic feasibility. The binding orientation

of the best designed compound 5 (Table 1, Figure 4) from FBDD approach,

is shown in Figure 5. It showed highest GFS of 72.5 kJ/mol and formed π-π

stacking interactions between the benzene ring of compound 5 and indole ring

of W84 (CS) in AChE enzyme (Figure 5). This result is in agreement with the

earlier reported AChE-donepezil complexes in which benzene ring of donepezil

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Int. J. Bioinformatics and Biological Sci.: v.2 n.1&2, p. 111-126. March & June 2014