Evaluation of novel Hyphodermin derivatives as Glycogen Phosphorylase a inhibitors

被引：14

作者：

Loughlin, Wendy A. ^{[1
,2
]}

Pierens, Gregory K. ^{[3
]}

Petersson, Maria J. ^{[1
]}

Henderson, Luke C. ^{[1
]}

Healy, Peter C. ^{[1
,2
]}

机构：

[1] Griffith Univ, Eskitis Inst Cell & Mol Therapies, Brisbane, Qld 4111, Australia

[2] Griffith Univ, Sch Biomol & Phys Sci, Brisbane, Qld 4111, Australia

[3] Univ Queensland, Gehrmann Labs, Ctr Magnet Resonance, Brisbane, Qld 4072, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 11期

关键词：

hyphodermin; glycogen phosphorylase a; inhibitor; hydrobenzoindole carboxylic acids; CLogP;

D O I：

10.1016/j.bmc.2008.04.047

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The lipophilicity, permeability, solubility, polar surface area and 'rule-of-five' properties were assessed, using QikProp v2.5 (Schrodinger, Inc.) and ALOGPS 2.1 calculations, for 25 Hyphodermin derivatives. These compounds obeyed the 'rule-of-five', and the calculated physicochemical values were generally within desired limits. All compounds were tested against Glycogen Phosphorylase a (GPa). Four phenyl and benzyl substituted 2-oxo-hexahydro and tetrahydrobenzo[cd]indole carboxylic acids were identified as novel inhibitors of GPa with estimated IC50 values in the range 0.8-1.3 mM. Molecular modelling of these novel inhibitors was used to obtain the main structural features of this class of molecule for future structure-activity relationship studies. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：6172 / 6178

页数：7

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