Please use this identifier to cite or link to this item: https://hdl.handle.net/1959.11/18491
Title: The effect of hydrophobicity upon the direct mutagenicity of N-acyloxy-N-alkoxyamides - bilinear dependence upon LogP
Contributor(s): Glover, Stephen  (author)orcid ; Schumacher, Rhiannon R (author)
Publication Date: 2016
Open Access: Yes
DOI: 10.1016/j.mrgentox.2015.11.005
Handle Link: https://hdl.handle.net/1959.11/18491
Abstract: N-Acyloxy-N-alkoxyamides 1 are direct-acting mutagens for which a bilinear QSAR has been established, which predicts with accuracy their activity in the Ames reverse mutation assay in 'Salmonella typhimurium' TA100, based upon their hydrophobicity (LogP), reactivity (pKA of the carboxylic acid of the N-carboxyl group) and TAFT steric parameters. From activity data for 55 congeners and incorporating five mutagens bearing long-chain hydrocarbons on the alkoxyl and acyloxyl groups, designed for this study, a maximal LogPo, is found to be LogP = 6.4. Mutagens with LogP < than this value show a linear hydrophobic dependence (h = 0.24) relating to their binding to bacterial DNA and those with LogP > LogPo undergo lipid entrapment which masks the DNA binding effect. The QSAR has been used to differentiate between lipophilicity and steric inhibition to groove binding in a series of outliers bearing large tert-butyl groups as well as to confirm the enhancement to DNA binding of the naphthalene moiety, which is shown to be equivalent to about 3.5 LogP units.
Publication Type: Journal Article
Source of Publication: Mutation Research: Genetic Toxicology and Environmental Mutagens, v.795, p. 41-50
Publisher: Elsevier BV
Place of Publication: Netherlands
ISSN: 1879-3592
1383-5718
Fields of Research (FoR) 2008: 030404 Cheminformatics and Quantitative Structure-Activity Relationships
030402 Biomolecular Modelling and Design
030401 Biologically Active Molecules
Fields of Research (FoR) 2020: 340404 Cheminformatics and quantitative structure-activity relationships
340402 Biomolecular modelling and design
340401 Biologically active molecules
Socio-Economic Objective (SEO) 2008: 970103 Expanding Knowledge in the Chemical Sciences
970106 Expanding Knowledge in the Biological Sciences
Socio-Economic Objective (SEO) 2020: 280105 Expanding knowledge in the chemical sciences
280102 Expanding knowledge in the biological sciences
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Appears in Collections:Journal Article
School of Science and Technology

Files in This Item:
6 files
File Description SizeFormat 
open/SOURCE03.pdfpre-peer review version (hidden)677.8 kBAdobe PDF
Download Adobe
View/Open
Show full item record

SCOPUSTM   
Citations

6
checked on Oct 5, 2024

Page view(s)

1,388
checked on Nov 12, 2023

Download(s)

400
checked on Nov 12, 2023
Google Media

Google ScholarTM

Check

Altmetric


Items in Research UNE are protected by copyright, with all rights reserved, unless otherwise indicated.