Abstract:
:We have performed a systematic study of the interaction of 36 di- and tri-phenylethylene derivatives (DPEs and TPEs) with protein kinase C (PKC). The results were submitted to a multivariate analysis in order to identify the structural features that might be implicated in interference with the activity of three PKC subspecies under three enzyme activation conditions. Four groups of test-compounds, each with common chemical features, could be distinguished clearly. The first group comprised all TPEs substituted with at least one basic dialkylaminoethoxy side-chain. These inhibited type alpha, beta and gamma PKC subspecies activated by Ca2+ and phosphatidylserine (PS) with or without diolein (DO) at micromolar concentrations but did not inhibit protamine sulfate phosphorylation. The other effectors, which all possessed a 1,1-bis-(p-hydroxyphenyl) ethylene moiety, influenced PKC activity at high concentrations (30-200 microM) and could be divided into two groups. One group constituted PKC inhibitors in the TPE series and inhibited PKC activated by Ca2+, PS and DO, as well as protamine sulfate phosphorylation. The other group constituted dual-type inhibitors/activators in the DPE series and stimulated PKC in the presence of Ca2+ and low PS concentrations but inhibited the enzyme in the simultaneous presence of DO. The fourth group of compounds was inactive and had, for the most part, one or two substituents with weak steric hindrance. In agreement with previous data for six lead compounds, this study suggests that, in these chemical series, a basic amino side-chain leads to interaction with phospholipid and the regulatory domain of PKC, whereas a 1,1-bis-(p-hydroxyphenyl) ethylene moiety leads to interaction with the catalytic domain of the enzyme.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Bignon E,Pons M,Doré JC,Gilbert J,Ojasoo T,Miquel JF,Raynaud JP,Crastes de Paulet Adoi
10.1016/0006-2952(91)90448-esubject
Has Abstractpub_date
1991-09-12 00:00:00pages
1373-83issue
7eissn
0006-2952issn
1873-2968pii
0006-2952(91)90448-Ejournal_volume
42pub_type
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journal_title:Biochemical pharmacology
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更新日期:1993-10-05 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.01.005
更新日期:2006-04-28 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.12.017
更新日期:2008-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0006-2952(85)90750-6
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pub_type: 杂志文章
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更新日期:2018-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:1982-04-15 00:00:00
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pub_type: 杂志文章
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更新日期:2003-02-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.12.020
更新日期:2011-03-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90494-0
更新日期:1985-04-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90537-0
更新日期:1988-05-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90096-4
更新日期:1990-12-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(00)00535-9
更新日期:2001-01-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00819-2
更新日期:1997-03-21 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.bcp.2018.06.028
更新日期:2018-09-01 00:00:00
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更新日期:2010-12-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-10-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2006.04.010
更新日期:2006-11-30 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2015.03.002
更新日期:2015-05-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2004.01.017
更新日期:2004-05-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.08.001
更新日期:2006-11-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90118-x
更新日期:1994-07-19 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(96)00693-4
更新日期:1997-01-10 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90109-1
更新日期:1985-01-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2008.11.017
更新日期:2009-03-01 00:00:00
abstract::LY83583 (6-anilino-5,8-quinolinedione), considered to be a relatively specific repressor of cyclic GMP formation, is shown in the present study to inhibit (K(i) = 3 microM) glutathione reductase from bovine intestinal mucosa. As glutathione disulphide has been reported to inhibit guanylate cyclase irreversibly [Braugh...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90236-p
更新日期:1993-06-22 00:00:00