Phytochemicals from Amberboa ramosa as potential DPP-IV inhibitors for the management of Type-II diabetes mellitus: Inferences from in-silico investigations

Diabetes is a chronic metabolic disorder, and as per the global burden, it is estimated that around 462 million people will be affected due to the cause of this disease. Currently, several drug treatments are available, but the need for herbal medicine is required for the management of diabetes. The present study focuses on the identification of potential compounds from the Amberboa ramosa plant and weed out similar potential compounds from a phytochemical library based on the best hits from the selected plant for the inhibition of dipeptidyl peptidase-IV (DPP-IV) enzyme using computational approaches. The results demonstrate that 3 beta,4 alpha,8 alpha-trihydroxy-4 beta-(hydroxymethyl)-1 alpha H,5 alpha H,6 beta H,7 alpha H-guai-10(14),11(13)-dien-6,12-olide (Compound 1) and 5-hydroxy-7,8-dimethoxyflavone (Compound 2) showed maximum binding energy and dock score among all the compounds obtained from A. ramosa whereas, NPC170675 (Compound 3) was obtained from the phytochemical library. The molecular dynamics reveal that among all the three compounds, the root mean square deviation (RMSD) of compound 3 was found to be stable after 20 ns throughout the simulation. Compound 2 from A. ramosa was found to be more stable as compared to compound 1 in the active site during the simulation of 100 ns. Among all the three phytocompounds, compound 2 possesses lowest Delta G(Bind) energy of -51.096 kcal/mol in the post-simulation binding free energy analysis. The molecular reactivity analysis using hybrid QMMM approach shows compound 2 has the highest softness value in both the free (6.410 eV) and bound (6.817 eV) states, as well as the lowest hardness (0.078 eV/0.073 eV) and HOMO-LUMO gap (0.156 eV), indicating that it is more reactive than the others. Hence, compound 2 from A. ramosa is the most validated ligand from the in-silico findings. Thus, the exploration of phytoconstituents from A. ramosa plant and phytochemical library could be used in the management of Type-II diabetes mellitus. (C) 2022 Published by Elsevier B.V.