黄酮类化合物具有多种生物学效应，从增强免疫力到抗癌和抗糖尿病等。结构改性的黄酮（SMC）在糖尿病和心脑血管代谢并发症的临床治疗中具有重要意义。从原始研究文章中筛选出14个具有结构修饰的目标明确、生物学出色的黄酮化合物，并将其引入本研究中。本研究通过网络药理学分析评估了SMC对糖尿病的影响。网络数据显示化合物S2、S3、S5、S9和S12适合糖尿病的靶点。特别是S5和S9化合物在TNF、PI3K、MAPK1和AKT1的活性位点上具有更高的结合亲和力。化合物S9（（E）-3-(4-(1H-咪唑-1-基)苯基)-1-(4-(2,4-二氟苯氧基)苯基)丙-2-烯-1-酮）被确定为对MAPK3（PDB:4QTB）活性位点具有更强的结合亲和力，为-10.5（千卡/摩尔）。为了提供更有效的蛋白质-配体相互作用机制，将分子模拟复合物（ERK2激酶-S5）在300K下进行了100 ns的分子动力学模拟。通过评估复合物的结构稳定性、紧致性、残留灵活性和氢键相互作用，证明了整合网络药理学、基于计算的虚拟筛选和分子对接分析能够有效发掘结构改性化合物，并有助于鉴定出治疗血糖控制的前导化合物。由Ramaswamy H. Sarma通讯。

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.