63 164

Cited 8 times in

Structural requirements for the neuroprotective effects of aspirin analogues against N-methyl-D-aspartate and zinc ion neurotoxicity.

Authors
Moon, HS; Nam, SI; Kim, SD; Kim, D; Gwag, BJ; Lee, YA; Yoon, SH
Citation
The Journal of pharmacy and pharmacology, 54(7):935-944, 2002
Journal Title
The Journal of pharmacy and pharmacology
ISSN
0022-35732042-7158
Abstract
In order to elucidate the structural requirements for the dual neuroprotective activity of aspirin against N-methyl-D-aspartate (NMDA) and zinc ion neurotoxicity, various aspirin analogues and derivatives, modified at the carboxylic group, the acetyl group, and the chain length between the carboxylic acid moiety and phenyl ring, were synthesized. Replacement of the carboxylic acid group with alkyl groups (compounds 2c and 2d) resulted in a dramatic increase in neuroprotective activity against NMDA neurotoxicity, while reduction of the carboxylic acid group to the alcohol (compound 2g) completely abolished this activity. In contrast to NMDA neurotoxicity, compounds that are devoid of the carboxylic acid group did not show any activity against zinc ion neurotoxicity. Replacement of the acetyl group with a propionyl (compound 5a) or butyryl group (compound 5b) did not significantly change the activity against NMDA neurotoxicity, but replacement of the acetyl group with a propionyl group (compound 5a) resulted in a slight decrease in activity against zinc ion neurotoxicity. Compound 12, which has ethylene units between the carboxylic acid moiety and phenyl ring in the structure of aspirin, exhibited greater neuroprotective activity against NMDA neurotoxicity than the compared compounds (aspirin, compound 9 and compound 17), which have different chain lengths. A similar trend was also observed in the neuroprotective activity against zinc ion neurotoxicity. These results indicate that the carboxylic acid group in aspirin is not indispensable for the inhibitory effect against NMDA neurotoxicity, but is essential for the inhibitory effect against zinc ion neurotoxicity. The acetyl group and ethylene unit's distance are favourable for the inhibitory effect against NMDA neurotoxicity as well as zinc ion neurotoxicity.
MeSH terms
AnimalsAnti-Inflammatory Agents, Non-Steroidal/chemistry/*pharmacologyAspirin/analogs & derivatives/chemistry/*pharmacologyCarboxylic Acids/chemistryCerebral Cortex/cytology/embryologyExcitatory Amino Acid Agonists/*toxicityIonsMiceMice, Inbred ICRN-Methylaspartate/*toxicityNeuroprotective Agents/chemistry/*pharmacologyZinc/*toxicity
DOI
10.1211/002235702760089054
PMID
12162712
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
곽, 병주
Files in This Item:
Full-Text Not Available.txtDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse