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

Abstract

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 via network pharmacology analysis. The network data shows compounds S2, S3, S5, S9 &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, in silico 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