國家衛生研究院 NHRI:Item 3990099045/4679
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    題名: Novel classes of inhibitors that suppress the nitric oxide production in RAW264.7 cells stimulated by LPS and IFN gamma
    其他題名: Novel classes of inhibitors that suppress the nitric oxide production in RAW264.7 cells stimulated by LPS and IFNγ
    作者: Tseng, H;Wu, S;Jiaang, W;Wang, S;Lee, S
    貢獻者: Division of Biotechnology and Pharmaceutical Research
    摘要: Three distinct isoforms of nitric oxide synthase (NOS), neural (nNOS), endothelial (eNOS), and inducible (iNOS), utilize the L-arginine andoxygen as co-substrates and convert them into L-citrulline and nitric oxide (NO). Among them, iNOS is induced to express and generate large quantity of nitric oxide upon the stimuli of endotoxins or cytokines for involving in pathological responses at the level of μM in contrast to pMfrom nNOS and eNOS. However, NO is a double-edged molecule. The improper overproduced NO by iNOS causes in acute and chronic inflammatory related diseases. Overproduction of NO by iNOS has been implicated in various pathological processes including septic shock,tissue damage following inflammation and rheumatoid arthritis. Selective inhibition of iNOS may be beneficial in various forms of shock and inflammation, where as inhibition of nNOS may protect against neuro-injury. Accordingly, selective inhibition of nNOS or iNOS versus eNOSmay provide a novel therapeutic approach to various diseases. A series of benzothiazolium compounds were identified as novel classes ofinhibitors of nitric oxide production generated by RAW264.7 cells stimulated by LPS/IFNγ. Compared to known inhibitors for nitric oxide production, herein we have identified 100 to 1000 fold more potent inhibitors with IC50 at ~50 nM to μM range compared to L-NMMA of IC5088.4uM in our system. The structure-activity relationship to elucidate the essential structural requirements has been described. In addition, most of effective compounds did not show significant cytotoxicity. The effective benzothiazolium compounds affect the iNOS protein expression and thus the nitric oxide production.
    日期: 2004-11
    關聯: Molecular Biology of the Cell. 2004 Nov;15(Suppl.S):497A.
    Link to: http://ascb.org/files/Past-AM-Meetings/2004_Abstracts.pdf
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1059-1524&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000224648802631
    顯示於類別:[李秀珠] 會議論文/會議摘要
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