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

Abstract

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-λ⁵‐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 α-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 α-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}‐1,3,2λ⁵‐dioxaphospholan‐2‐one (6j) (IC₅₀, 94.3 ± 0.5 μg/mL) and 1‐methyl‐6‐[(2‐oxo‐4‐{[(9H‐purin‐9‐yl)methoxy]methyl}‐1,3,2λ⁵‐dioxaphospholan‐2‐yl)amino]‐1,2,3,4‐tetrahydropyrimidine‐2,4‐dione (6f) (IC₅₀, 99.0 ± 0.4 μg/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 μg/mL when compared with the standard drug, acarbose (IC₅₀, 50.47 ± 0.28 μg/mL).

Graphical Abstract

Keywords:

• Phosphorylated derivatives
• purine
• molecular docking
• α-amylase
• acarbose

Acknowledgments

The authors thank Prof. W. Rajendra, Division of Molecular Biology, Department of Zoology, S. V. University, Tirupati for his support in biological activity studies. The authors also acknowledge Dr. C. Naga Raju, Department of Chemistry, S. V. University, Tirupati for his constant support to complete this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).