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
收藏
页码：6172 / 6178
页数：7
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