Integrated in vitro and in silico evaluation of adamantane-1,2,3-triazole hybrids as potential α-glucosidase inhibitors.

Aims

To find for lead compounds, efficiently defeating diabetes mellitus, prompted us to the synthesis of a new library of adamantane‑appended 1,2,3-triazole hybrid conjugates (AT1-AT18). MATERIAL AND

Methods

The current synthesis of adamantane-appended 1,2,3-triazoles was performed by using Cu(I)-catalyzed azide-alkyne cycloaddition reaction. The hybrids were structurally characterized via 1H, 13C NMR, FTIR, and mass spectrometry. The hybrids were evaluated for their inhibitory potential for α-glucosidase enzyme, along with in silico activity, i.e., molecular docking, molecular dynamics simulations, and ADME (absorption, distribution, metabolism, and excretion).

Results

Hybrid AT5 (IC50 5.5 ± 0.87 µM) showed maximum inhibition potential against α-glucosidase enzyme, which may be risen from the methyl substitution on phenyl ring. The results were compared with the reference, acarbose (IC50 13.5 ± 0.32 µM). The docking studies using PDB:3L4U revealed that the hybrid AT5 demonstrated a docking score -7.656, which was better than alkyne, i.e., -3.894. Ligand stability analysis explored by using molecular dynamics demonstrated the useful findings such as RMSD <2 Å, 0-2 H-bonds, for hybrid AT5, highlighting the stabilization contribution of triazole unit.

Conclusion

The hybrid AT5 may be used as potential lead compound after necessary structural modifications.