Development of QSARs to investigate the bacterial toxicity and biotransformation potential of aromatic heterocyclic compounds

J. G. Bundy, A. Morriss, D. G. Durham, D. G. Campbell, Graeme Iain Paton

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

A series of aromatic heterocyclic and hydrocarbon compounds were tested for toxicity and biotransformation potential against two contrasting lux-marked whole-cell microbial biosensors. Toxicity was determined by inhibition of light output of a Pseudomonas fluorescens construct that expresses lux constitutively. Biotransformation was tested by increase in light output of P. flourescens HK44 (pUTK21), which expresses lux when in the presence of a metabolic intermediate (salicylate). The data were then modelled against physical/chemical properties of the compounds tested to see if quantitative structure-activity relationships (QSARs) could be derived. Toxicity was found to be accurately predicted by log K-ow (R-2 = 0.95, Q(2) = 0.88), with the basic (pyridine-ring containing) heterocycles modelled separately. The biotransformation data were best modelled using lowest unoccupied molecular orbital (LUMO) energies (R-2 = 0.90, Q(2) = 0.87). (C) 2001 Elsevier Science Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)885-892
Number of pages7
JournalChemosphere
Volume42
DOIs
Publication statusPublished - 2001

Keywords

  • structure-activity relationship
  • NAH plasmid
  • biosensor
  • Lux fusion
  • PSEUDOMONAS-FLUORESCENS
  • BIODEGRADATION
  • NAPHTHALENE
  • PHENANTHRENE
  • ECOTOXICITY
  • DEGRADATION
  • CATABOLISM
  • TOXICOLOGY
  • ANTHRACENE
  • NARCOSIS

Cite this

Development of QSARs to investigate the bacterial toxicity and biotransformation potential of aromatic heterocyclic compounds. / Bundy, J. G.; Morriss, A.; Durham, D. G.; Campbell, D. G.; Paton, Graeme Iain.

In: Chemosphere, Vol. 42, 2001, p. 885-892.

Research output: Contribution to journalArticle

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AU - Morriss, A.

AU - Durham, D. G.

AU - Campbell, D. G.

AU - Paton, Graeme Iain

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AB - A series of aromatic heterocyclic and hydrocarbon compounds were tested for toxicity and biotransformation potential against two contrasting lux-marked whole-cell microbial biosensors. Toxicity was determined by inhibition of light output of a Pseudomonas fluorescens construct that expresses lux constitutively. Biotransformation was tested by increase in light output of P. flourescens HK44 (pUTK21), which expresses lux when in the presence of a metabolic intermediate (salicylate). The data were then modelled against physical/chemical properties of the compounds tested to see if quantitative structure-activity relationships (QSARs) could be derived. Toxicity was found to be accurately predicted by log K-ow (R-2 = 0.95, Q(2) = 0.88), with the basic (pyridine-ring containing) heterocycles modelled separately. The biotransformation data were best modelled using lowest unoccupied molecular orbital (LUMO) energies (R-2 = 0.90, Q(2) = 0.87). (C) 2001 Elsevier Science Ltd. All rights reserved.

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KW - Lux fusion

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KW - BIODEGRADATION

KW - NAPHTHALENE

KW - PHENANTHRENE

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