In silico molecular docking study, synthesis and α-amylase inhibitory activity evaluation of phosphorylated derivatives of purine

A series of phosphorylated derivatives of purine were synthesized in good yields (88-95%) by the reaction of 2-chloro-4-{[(9H-purin-9-yl)methoxy]methyl}-1,3,2-lambda(5)-dioxaphospholan-2-one with various heterocyclic amines. In silico molecular docking study was performed for all the designed compounds to assess their potential ability to inhibit the pancreatic alpha-amylase enzyme. The compounds (6a-j) with good inhibition toward the target enzyme were prompted for the synthesis. Spectroscopic analyses of all the newly synthesized compounds were performed to confirm their structures. In vitro alpha-amylase inhibitory activity of the synthesized compounds was also carried out using acarbose as a standard drug. The compounds 2-[(6-chloro-1,3-benzothiazol-2-yl)amino]-4-{[(9H-purin-9-yl)methoxy]methyl}-1,3,2 lambda(5)-dioxaphospholan-2-one (6j) (IC50, 94.3 +/- 0.5 mu g/mL) and 1-methyl-6-[(2-oxo-4-{[(9H-purin-9-yl)methoxy]methyl}-1,3,2 lambda(5)-dioxaphospholan-2-yl)amino]-1,2,3,4-tetrahydropyrimidine-2,4-dione (6f) (IC50, 99.0 +/- 0.4 mu g/mL) reported the highest inhibition among the synthesized compounds. All the remaining compounds exhibited good to moderate inhibition with IC50 values in the range of 102.9 +/- 0.6 to 233.5 +/- 0.6 mu g/mL when compared with the standard drug, acarbose (IC50, 50.47 +/- 0.28 mu g/mL). [GRAPHICS] .