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Evaluation of novel hyphodermin derivatives as glycogen phosphorylase a inhibitors

journal contribution
posted on 2008-06-01, 00:00 authored by W Loughlin, G Pierens, M Petersson, Luke HendersonLuke Henderson, P Healy
The lipophilicity, permeability, solubility, polar surface area and ‘rule-of-five’ properties were assessed, using QikProp v2.5 (Schrödinger, 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.

History

Journal

Bioorganic & medicinal chemistry

Volume

16

Issue

11

Pagination

6172 - 6178

Publisher

Pergamon

Location

Oxford, England

ISSN

0968-0896

eISSN

1464-3391

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2008, Elsevier Ltd.