Chalcones reloaded: an integration of network pharmacology and molecular docking for type 2 diabetes therapy

Chalcones have various biological effects, from immune boosting to anti-cancer and anti-diabetic. Structurally modified chalcones (SMC) are clinically relevant for diabetes and cardiometabolic complications. From the original research articles, a structurally proven and biologically outstanding 14 structurally modified chalcones were screened and inducted in this study. This study evaluated the effects of SMC towards diabetes <i>via</i> network pharmacology analysis. The network data shows compounds S2, S3, S5, S9 &amp;S12 suit the diabetes target. Especially Compounds S5 and S9 have a higher binding affinity towards the targets of TNF, PI3K, MAPK1 and AKT1 active sites. Compound S9 [(E)-3-(4-(1H-imidazol-1-yl)phenyl)-1-(4-(2,4-difluorobenz-yloxy)phenyl)prop-2-en-1-one] have identified with stronger binding affinities towards the active sites of MAPK3 (PDB:4QTB) −10.5(Kcal/mol). To provide a more effective mechanism for demonstrating protein-ligand interaction, one of the molecular docking complex (ERK2 kinase-S5) was subjected to a molecular dynamic at 300K for 100 ns. In term of structural stability, structure compactness, residual flexibility and hydrogen bond interaction of the complex was evaluated Integrating network pharmacology, <i>in silico</i> virtual screening, and molecular docking analysis shows that structurally modified compounds are effective and may help identify lead compounds towards glycemic control. Communicated by Ramaswamy H. Sarma