Syntheses And Evaluation Of Asymmetric Curcumin Analogues As Potential Multifunctional Agents For The Treatment Of Alzheimer's Disease.
A series of new asymmetric curcumin analogues were synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. Our results showed that most of these synthetic compounds had better inhibitory properties against Aβ aggregation compared with curcumin, and better anti-oxidative properties compared with the reference compound Trolox through the study of oxygen radical absorbance capacity (ORAC). Some compounds showed good properties in selectively chelating metal ions such as copper and iron. Besides, some compounds were found to be able to dissociate Aβ protein which had already aggregated. The structure-activity relationships (SAR) of these synthetic compounds were studied. The present investigation indicated that our synthetic asymmetric curcumin derivatives could be potential multifunctional agents for the treatment of Alzheimer's disease (AD).
Peng
P
Zhai
Chun-Li
CL
Xia
Jia-Heng
JH
Tan
Ding
D
Li
Tian-Miao
TM
Ou
Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China. lsshsl@mail.sysu.edu.cn.
Shi-Liang
SL
Huang
Lian-Quan
LQ
Gu
Zhi-Shu
ZS
Huang
D000544:Alzheimer Disease / Q000188:drug therapy*; D000682:Amyloid / Q000187:drug effects / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology; D003300:Copper / Q000378:metabolism; D003474:Curcumin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D004341:Drug Evaluation; D006801:Humans; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D010100:Oxygen / Q000737:chemistry; D010446:Peptide Fragments / Q000378:metabolism; D066329:Protein Aggregates / Q000187:drug effects; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D000682:Amyloid; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002614:Chelating Agents; D002839:Chromans; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42); D003300:Copper; D003474:Curcumin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D010100:Oxygen