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Article: Neuroactive flavonoids interacting with GABA A receptor complex

TitleNeuroactive flavonoids interacting with GABA A receptor complex
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2005
Citation
Current Drug Targets: Cns And Neurological Disorders, 2005, v. 4 n. 5, p. 575-585 How to Cite?
AbstractClassical benzodiazepines (BZs) are the most widely prescribed drugs acting on the central nervous system (CNS). They exert their therapeutic effects via binding to the BZ-site of GABA A receptors, and allosterically modulating the chloride flux through the ion channel complex. Given the multiple actions of classical BZs, the serious limitations to their usefulness have directed much research into development of novel ligands for the BZ-site with retained therapeutic effectiveness and minimal side effects. From the studies of CNS-active chemical constituents of medicinal herbs, some members of the family of flavonoids were demonstrated to have moderate binding affinities for the BZ-site. In vivo studies revealed that these compounds were mostly partial agonists of GABA A receptors, and only a few flavonoids were shown to possess antagonistic activities. At effective anxiolytic doses, the actions of partial agonistic flavonoids were often not accompanied by sedative and myorelaxant side effects. Based on structure-activity relationship (SAR) studies, incorporation of electronegative groups to the C6 and C3′ on the flavone backbone was found to yield significant increases in the binding affinities for the BZ-site. It was also shown that 2′-hydroxyl was a critical moiety on flavonoids with regard to BZ-site binding. These have guided the identification of several synthetic flavonoids with high BZ-site binding affinity and in vivo activity, and further quantitative SAR studies resulted in the development of several pharmacophore models. This review attempts to summarize these findings, which has led to the establishment of flavonoids as potential therapeutics for GABA A receptor-mediated disorders. © 2005 Bentham Science Publishers Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/90955
ISSN
References

 

DC FieldValueLanguage
dc.contributor.authorWang, Fen_HK
dc.contributor.authorHuen, MSYen_HK
dc.contributor.authorTsang, SYen_HK
dc.contributor.authorXue, Hen_HK
dc.date.accessioned2010-09-17T10:10:53Z-
dc.date.available2010-09-17T10:10:53Z-
dc.date.issued2005en_HK
dc.identifier.citationCurrent Drug Targets: Cns And Neurological Disorders, 2005, v. 4 n. 5, p. 575-585en_HK
dc.identifier.issn1568-007Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/90955-
dc.description.abstractClassical benzodiazepines (BZs) are the most widely prescribed drugs acting on the central nervous system (CNS). They exert their therapeutic effects via binding to the BZ-site of GABA A receptors, and allosterically modulating the chloride flux through the ion channel complex. Given the multiple actions of classical BZs, the serious limitations to their usefulness have directed much research into development of novel ligands for the BZ-site with retained therapeutic effectiveness and minimal side effects. From the studies of CNS-active chemical constituents of medicinal herbs, some members of the family of flavonoids were demonstrated to have moderate binding affinities for the BZ-site. In vivo studies revealed that these compounds were mostly partial agonists of GABA A receptors, and only a few flavonoids were shown to possess antagonistic activities. At effective anxiolytic doses, the actions of partial agonistic flavonoids were often not accompanied by sedative and myorelaxant side effects. Based on structure-activity relationship (SAR) studies, incorporation of electronegative groups to the C6 and C3′ on the flavone backbone was found to yield significant increases in the binding affinities for the BZ-site. It was also shown that 2′-hydroxyl was a critical moiety on flavonoids with regard to BZ-site binding. These have guided the identification of several synthetic flavonoids with high BZ-site binding affinity and in vivo activity, and further quantitative SAR studies resulted in the development of several pharmacophore models. This review attempts to summarize these findings, which has led to the establishment of flavonoids as potential therapeutics for GABA A receptor-mediated disorders. © 2005 Bentham Science Publishers Ltd.en_HK
dc.languageengen_HK
dc.relation.ispartofCurrent Drug Targets: CNS and Neurological Disordersen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.subject.meshAnalysis of Varianceen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBenzodiazepines - agonists - antagonists & inhibitorsen_HK
dc.subject.meshCentral Nervous System - drug effects - metabolismen_HK
dc.subject.meshDrugs, Chinese Herbal - chemistry - metabolism - pharmacologyen_HK
dc.subject.meshFlavonoids - chemistry - metabolism - pharmacologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMedicine, Chinese Traditionalen_HK
dc.subject.meshReceptors, GABA-A - drug effects - metabolismen_HK
dc.subject.meshStructure-Activity Relationshipen_HK
dc.titleNeuroactive flavonoids interacting with GABA A receptor complexen_HK
dc.typeArticleen_HK
dc.identifier.emailHuen, MSY:huen.michael@hku.hken_HK
dc.identifier.authorityHuen, MSY=rp01336en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.2174/156800705774322030en_HK
dc.identifier.pmid16266290-
dc.identifier.scopuseid_2-s2.0-26844489782en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-26844489782&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume4en_HK
dc.identifier.issue5en_HK
dc.identifier.spage575en_HK
dc.identifier.epage585en_HK
dc.identifier.scopusauthoridWang, F=36068003900en_HK
dc.identifier.scopusauthoridHuen, MSY=23004751500en_HK
dc.identifier.scopusauthoridTsang, SY=7102255989en_HK
dc.identifier.scopusauthoridXue, H=35235981600en_HK
dc.identifier.citeulike337946-

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