Preparation of two sets of 5,6,7-trioxygenated dihydroflavonol derivatives as free radical scavengers and neuronal cell protectors to oxidative damage.
An unusual class of 5,6,7-trioxygenated dihydroflavonols (3a-e and 4a-j) were designed and prepared. Their antioxidative properties were assessed by examining their capacities in several in vitro models, including superoxide anion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, rat liver homogenate lipid peroxidation inhibition, PC12 cells protection from oxidative damage, and xanthine oxidase inhibition. These dihydroflavonols displayed positive quenching abilities towards O(2)(-) and DPPH free radicals, in which the majority exhibited superior antioxidant properties to Vitamin C. cis-Configurated compound (+/-)-3e demonstrated remarkable inhibition to LPO with an IC(50) value of 1.9+/-0.3 microM, which was apparently stronger than that of quercetin (IC(50)=6.0+/-0.4 microM). trans-Configurated dihydroflavonol (+/-)-4h exhibited significant protective effect on PC12 cells against oxidative damage with an EC(50) value of 41.5+/-5.3 microM, more effective compared to that of quercetin (EC(50)=81.8+/-8.7 microM). The 6-OH-5,7-dimethoxy analogue (+/-)-3d showed significant inhibition of xanthine oxidase with an IC(50) value of 16.0+/-0.8 microM, which is superior to that of allopurinol (IC(50)=23.5+/-2.0 microM). In addition to the hypothesized action mechanism of the bio-active compounds, 3D modeling was used to analyze the relationship between the minimized-energy structures and antioxidant activities.
Key Laboratory of Southern Zhejiang TCM R&D, Pharmacy School of Wenzhou Medical College, Chashan District, Wenzhou, China.
Jingxu
J
Gong
Kexin
K
Huang
Feng
F
Wang
Leixiang
L
Yang
Yubing
Y
Feng
Haibo
H
Li
Xiaokun
X
Li
Su
S
Zeng
Xiumei
X
Wu
Joachim
J
Stöckigt
Yu
Y
Zhao
Jia
J
Qu
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D044948:Flavonols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008958:Models, Molecular; D008968:Molecular Conformation; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000975:Antioxidants; D044948:Flavonols; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014969:Xanthine Oxidase