Pyridinium Oxime Compounds as Antimicrobial Agents

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Authors
  1. Berger, B.J.
  2. Knodel, M.H.
Corporate Authors
Defence R&D Canada - Suffield, Ralston ALTA (CAN)
Abstract
Pyridinium oxime compounds have been utilised by a number of military organisations as one of the antidotes for nerve-agent poisoning. In Canada, the preferred compound from this class is HI-6 [1-[((4-carbomylpyridino)methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium dichloride or dimethanesulfonate], which has been demonstrated to be tolerated at high doses without significant ill effects. In this study, HI-6 and 15 structural analogues have been examined for their antimicrobial properties against a series of model organisms: Bacillus cereus and B. anthracis Sterne (as models for virulent B. anthracis), Ochrobactrum intermedium (as a model for Brucella spp.), Mycobacterium marinum (as a model for M. tuberculosis), and Crithidia luciliae (as a model for Leishmania spp.). In general, the compounds were found to have little to no antimicrobial effect, with KJD-2-11, a thiourea derivative, being the most active in all the test systems. This analogue had an IC50 of 350 µM against B. cereus in a rich medium and 80µM against B. anthracis Sterne in a minimal defined medium, 720 µM against O. intermedium, 28 µM against M. marinum, and 27 µM against C. luciliae. In contrast, HI-6 had an IC50 of 69 µM against M. marinum, but had no detectable effect on any other organism up to the maximum tested concentration (1.0 or 10 mM). The results of this study indicate that the pyridinium oxime compounds already used as nerve-agent antidotes will have no antimicrobia

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Keywords
Antimicrobial agents;Antibiotic sensitivity
Report Number
DRDC-SUFFIELD-TM-2007-176 — Technical Memorandum
Date of publication
01 Aug 2007
Number of Pages
33
DSTKIM No
CA029700
CANDIS No
528143
Format(s):
CD ROM

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