In silico design, synthesis and characterization of quercetin derivatives as anti-diabetic agents

Diabetes mellitus is a dominant metabolic condition noticeable by determined high blood sugar levels, stanching from either poor insulin production or insulin resistance. Managing diabetes often includes hindering enzymes, such as alphaamylase and alpha-glucosidase to control blood glucose points after meals. Natural polyphenols, such as quercetin, have proved major enzyme inhibitory activity, leading to developing interest in reviewing quercetin derivatives as prospective antidiabetic agents. This research emphasizes on the design, synthesis, and assessment of quercetin ester derivatives for their antidiabetic activity by means of in silico docking studies. The key area is to investigate the binding affinity of these derivatives to indispensable enzymes involved in carbohydrate metabolism, while also assessing their drug-likeness and toxicity features. Quercetin ester derivatives, EQ1 and EQ3, were produced through esterification reactions. Quercetin was reacted with benzoic acid and gallic acid, in that order, in toluene, using hydrochloric acid as a catalyst under reflux settings. To calculate the binding affinities, in silico docking studies were supported with human pancreatic alpha-amylase (PDB ID: 2QV4) and acid alpha-glucosidase (PDB ID: 5NN8). Drug-likeness was explored according to Lipinski's Rule of Five, and toxicity was projected by computational modeling procedures. Docking studies showed that EQ1 and EQ3 had concrete binding affinities for alpha-amylase and alphaglucosidase, exceeding the standard drug acarbose. EQ1 attained the highest docking score, with essential interactions such as hydrogen bonding and pi-pi stacking. Drug-likeness evaluation revealed no major rule violations, indicating favorable oral bioavailability for both compounds. Furthermore, toxicity predictions confirmed that EQ1 and EQ3 are non-toxic, underscoring their potential safety. The synthesized quercetin derivatives, EQ1 and EQ3, exhibit considerable promise as antidiabetic agents by inhibiting key enzymes. Their strong binding affinities, favorable drug-likeness characteristics, and non-toxic profiles highlight their potential for further biological studies to validate their effectiveness and therapeutic value in diabetes management.