Development of QSARs to investigate the bacterial toxicity and biotransformation potential of aromatic heterocylic compounds.
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. fluorescens 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 Kow (R2 = 0.95, Q2 = 0.88), with the basic (pyridine-ring containing) heterocycles modelled separately. The biotransformation data were best modelled using lowest unoccupied molecular orbital (LUMO) energies (R2 = 0.90, Q2 = 0.87).
Department of Plant and Soil Science, University of Aberdeen, UK. j.bundy@ic.ac.uk
J G
JG
Bundy
A W
AW
Morriss
D G
DG
Durham
C D
CD
Campbell
G I
GI
Paton
D001711:Biotransformation; D005453:Fluorescence; D005544:Forecasting; D006573:Heterocyclic Compounds, 1-Ring / Q000378:metabolism* / Q000633:toxicity*; D006841:Hydrocarbons, Aromatic / Q000378:metabolism* / Q000633:toxicity*; D010957:Plasmids; D011551:Pseudomonas fluorescens; D011725:Pyridines / Q000737:chemistry; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods
D006573:Heterocyclic Compounds, 1-Ring; D006841:Hydrocarbons, Aromatic; D011725:Pyridines