黄酮类化合物抑制β-酮酰基-ACP还原酶的构效关系研究OA北大核心CSTPCD

To study the relationship between the inhibitory ability of flavonoids against β-ketoacyl-acyl reductase(FabG)and the molecular structures,and the inhibitory mechanism was discussed.The inhibitory activities of 33 flavonoid compounds against FabG were systematically assessed by in vitro enzyme activity assay,and the structure-activity relationship was discussed.The inhibitory mode of flavonoids on FabG was investigated through molecular docking method and inhibition characteristics were also studied.At the mass concentration of 25 mg/L,the inhibition rates of isoginkgetin,orobol,and luteolin on FabG were more than 50％.Additionally,the inhibition rates of 15 other flavonoid compounds were more than 20％.The basic structural characteristics of flavonoids with FabG inhibitory activity were that the concurrent existence of hydroxy groups at positions C-5 and C-7 of the A ring as well as C-4'position the B ring,and the C ring had carbonyl group at position C-4 and double bond between positions C-2 and C-3.Moreover,the increase of ortho-hydroxyl substitution in the B-ring could enhance the compound's FabG inhibitory activity,whereas the hydroxylation of the C-3 position in the C ring resulted in a reduction of its inhibitory capacity.Molecular docking experiments indicated that the flavonoids could bind to the key active amino acid residues such as tyrosine-151(Tyr-151)and serine-138(Ser-138)of the FabG/NADP+complex through hydrogen bonds,π interaction and other binding forces.Furthermore,the inhibition kinetics results indicated that flavonoids inhibited FabG in a competitive relationship with substrate(EAA)and anti-competitive relationship with coenzyme(NADPH).Flavonoids exhibited inhibitory effects on FabG by binding to the FabG-NADP+complex and competing with the substrate for active sites.The inhibitory activity of flavonoids on FabG was intricately linked to their molecular structures,and the main active groups were hydroxyl substituents on rings A and B.