The synthesis and evaluation of novel hydroxyl substituted chalcone analogs with in vitro anti-free radicals pharmacological activity and in vivo anti-oxidation activity in a free radical-injury Alzheimer's model.
Alzheimer's disease (AD) pathogenesis involves an imbalance between free radical formation and destruction. In order to obtain a novel preclinical anti-AD drug candidate, we synthesized a series of novel hydroxyl chalcone analogs which  possessed anti-free radical activity, and screened their effects on scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and OH free radicals in vitro. Compound C7, 4,2'-dihydroxy-3,5-dimethoxychalcone was found to have potent activity in these anti-free radical activity tests. Further research revealed that C7 could elevate glutathione peroxidase (GSH-PX) and super oxide dismutase (SOD) levels and lower malonaldehyde (MDA) level in vivo in the Alzheimer's model. The indication of C7's effect on AD needs further study.
Department of Chemistry, Shantou University Medical College, Shantou 515041, Guangdong, China.
Ying
Y
Pan
Yicun
Y
Chen
Qingnan
Q
Li
Xiaoyu
X
Yu
Jinzhi
J
Wang
Jinhong
J
Zheng
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D001577:Benzophenones / Q000737:chemistry; D001713:Biphenyl Compounds / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002599:Chalcone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006900:Hydroxylation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D010851:Picrates / Q000378:metabolism; D012601:Scopolamine; D013482:Superoxide Dismutase / Q000378:metabolism
D001577:Benzophenones; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D005609:Free Radicals; D010851:Picrates; C052932:exifone; D008315:Malondialdehyde; D002599:Chalcone; C004931:1,1-diphenyl-2-picrylhydrazyl; D012601:Scopolamine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase