| Chromones are a group of oxygen-containing heterocyclic compounds with a benzene-γ-pyrone skeleton,which exists widely in plants and has many pharmacological effects.Agarwood,named for its sinking and fragrant properties when placed in water,is a traditional and valuable Chinese medicine.2-(2-Phenylethyl)chromone is the main active component of agarwood,which is mostly isolated from agarwood and is rarely found in other plants,hence it is referred to as agarwood chromone.This type of compound has various biological activities,including anticancer,antioxidant,anti-inflammatory,antibacterial,neuroactive,and hypoglycemic effects.In this study,based on the previous isolation and synthesis of agarwood chromone,we modified its structure to discover compounds with higher activity.A series of derivatives were synthesized by introducing amide groups into the 2-position of chromone and characterized by NMR,IR,MS,melting point,etc.The hypoglycemic and bacterial biofilm inhibition assays were also performed.1.Six different substituted chromone-2-carboxylic acids were synthesized by Kostanecki reaction using ortho-hydroxyacetophenone and its derivatives as starting materials,followed by cyclization and hydrolysis under acidic conditions.These chromone-2-carboxylic acids were then converted into 30 chromone-2-carboxamide derivatives by amidation with various amino compounds,among which 22 were newly synthesized compounds.The synthetic method was optimized,and the structures of the compounds were characterized by NMR,IR,high-resolution mass spectrometry(HRMS),and other techniques.2.In vitro HepG2 cell experiments showed that the synthesized compounds generally had antitumor activity and promising prospects for studying other biological activities.A high blood glucose mouse model was established by intraperitoneal injection of streptozotocin(dose 150 mg/kg),and the compounds were administered to mice by a single subcutaneous injection(dose 120 mg/kg).After 2 hours,blood glucose levels were measured.The experimental results showed that compounds C3,C5,D2,D3,D4,D6,and F1 had good hypoglycemic effects on high blood glucose mice.The blood glucose lowering rates were 133.68 %,28.07 %,30.4 %,67.26 %,40.25 %,54.23 %,and 74.52 %,respectively.3.The biofilm inhibition effect of the synthesized compounds on Staphylococcus aureus and Pseudomonas aeruginosa was evaluated.It was found that at a concentration of 40 μmol/L,compounds C6,D5,and E6 had inhibitory rates of 80.8 %,77 %,and 70.6 %,respectively,against S.aureus biofilm,while compounds B5,D5,and C3 had inhibitory rates of 70.8 %,67.5 %,and 67.3 %,respectively,against P.aeruginosa biofilm,with significant biofilm elimination effects.Most of the remaining compounds also showed some degree of inhibition against S.aureus and P.aeruginosa biofilms.However,these compounds did not show significant inhibitory effects against other bacteria such as Bacillus subtilis,Escherichia coli,and Candida albicans.4.Molecular docking experiments indicated that compounds B5,C3,and D5 may interact with the key target Pqs R involved in controlling the formation of P.aeruginosa biofilms,competing with the native signal PQS for binding to the PqsR target and inhibiting biofilm formation. |
