Synthesis, biological activity, and QSAR studies of antimicrobial agents containing biguanide isosteres

Wernert, G, Winkler, D, Holan, G and Nicoletti, G 2004, 'Synthesis, biological activity, and QSAR studies of antimicrobial agents containing biguanide isosteres', Australian Journal of Chemistry, vol. 57, no. 1, pp. 77-85.


Document type: Journal Article
Collection: Journal Articles

Title Synthesis, biological activity, and QSAR studies of antimicrobial agents containing biguanide isosteres
Author(s) Wernert, G
Winkler, D
Holan, G
Nicoletti, G
Year 2004
Journal name Australian Journal of Chemistry
Volume number 57
Issue number 1
Start page 77
End page 85
Total pages 9
Publisher CSIRO Publishing
Abstract Analogues of chlorhexidine and chemically related antimicrobial compounds were synthesized, based on a model in which the bisbiguanide moieties were replaced by conformationally restricted cyclic isosteres. This model was tested by measuring the antimicrobial activities of the compounds. Quantitative structure-activity relationship (QSAR) studies showed a parabolic dependence of antimicrobial activity on the lipophilicity of the compounds. The basicity of the functional groups in the molecules was also very important, as uncharged molecules were not able to disrupt the microbial phospholipid bilayer and cause an antimicrobial effect. We compared our QSAR results to those reported in other studies of antimicrobials of diverse structure. We found very similar QSAR models for all compounds studies with a log P (octanol/water partition constant) optimum at 5.5 (neutral log P value). The form of the QSAR equations were similar, suggesting a common mode of action for these agents.
Subject Biologically Active Molecules
Keyword(s) chlorhexidine
antimicrobial compounds
bisbiguanide
cyclic isosteres
quantitative structure-activity relationship
DOI - identifier 10.1071/CH03146
ISSN 0004-9425
Versions
Version Filter Type
Citation counts: Scopus Citation Count Cited 9 times in Scopus Article | Citations
Altmetric details:
Access Statistics: 139 Abstract Views  -  Detailed Statistics
Created: Mon, 06 Dec 2010, 11:15:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us