Synthesis, α-amylase inhibitory activity evaluation and in silico molecular docking study of some new phosphoramidates containing heterocyclic ring

Abstract

We have synthesized a series of phosphoramidates containing a heterocyclic moiety with good yields (88–95%) by the reaction of (E)-5-benzylidene-3-((2-hydroxyethoxy)methyl)thiazolidine-2,4-dione with ethyl phosphorodichloridate followed by the reaction with various heterocyclic amines. The designed compounds were primarily screened for their ability to inhibit pancreatic α-amylase enzyme using in silico molecular docking approach. The compounds with good binding energies (−8.0 to −6.9 kcal/mol) when compared with standard drug, acarbose (−8.0 kcal/mol) were prompted for the synthesis. The structures of the newly prepared compounds were confirmed by their spectroscopic analyses. They were further screened in vitro for their inhibition toward α-amylase enzyme using acarbose as standard drug. All compounds exhibited moderate to good inhibition potential with IC₅₀ values in the range of 54.14 ± 0.35 to 185.04 ± 0.53 µg/mL when compared with the standard drug (IC₅₀, 50.47 ± 0.28 µg/mL). Especially, the compound (E)-2-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methoxy)ethyl ethyl 1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-ylphosphoramidate (6f) (IC₅₀, 54.14 ± 0.35 µg/mL) and (E)-2-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methoxy)ethyl ethyl benzo[d]thiazol-2-ylphosphoramidate (6c) (IC₅₀, 57.02 ± 0.32 µg/mL) exhibited the best inhibition among the synthesized compounds.

Graphical abstract

Keywords:

• Phosphoramidates
• thiazolidine-2,4-dione
• α-amylase
• acarbose
• molecular docking approach

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 to Dr. C. Naga Raju, Department of Chemistry, S. V. University, Tirupati, for his constant support to complete this work.

Disclosure statement

The authors declare no conflict of interest.