Toxicology of benzyl alcohols: a QSAR analysis.
There is an evidence that benzyl alcohols may exhibit toxicity via a radical mechanism. To test this possibility, we studied the toxicity of para substituted benzyl alcohols on rapidly dividing cancer cells (L1210 leukemia). This system has previously found utility in studying the apparent radical toxicity of a variety of phenols. However, no evidence could be found for an electronic effect and the cellular toxicity was associated primarily with hydrophobicity. Comparison of this quantitative structure-activity relationships (QSAR) with others for the reactions of benzyl alcohols in diverse systems provides insight into mechanisms of action. A QSAR for the interaction of benzyl alcohols with protozoa yields an equation that is dependent on both hydrophobicity and acidity of the OH group versus a mixture of bacteria and fungi, the critical dependence on hydrophobicity prevails with a small dependence on a resonance-stabilized, radical mediated electronic effect. The chloramphenicols provide an instructive example, where the radical mediated electronic effect overshadows the hydrophobic contribution to bacterial toxicity. These various QSAR for benzyl alcohols indicate that mechanisms of growth inhibition in vitro vary depending on cell/organism type, the strength of the bond and lability of the hydrogen, and the strength of the initiating radical reagent.
Kapur
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S
Department of Chemistry, Pomona College, Claremont, CA 91711, USA.
Shusterman
A
A
Verma
R P
RP
Hansch
C
C
Selassie
C D
CD
D000818:Animals; D001592:Benzyl Alcohols / Q000737:chemistry* / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D005609:Free Radicals; D007939:Leukemia L1210 / Q000473:pathology; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics; D018675:Toxicity Tests
D001592:Benzyl Alcohols; D005609:Free Radicals