Clastogenicity of triazinoindole derivatives in relation with the physicochemical properties of the substituents.
The clastogenicity of four compounds of the series 3-(4'-substituted-benzylidenamino)5H-1,2,3-triazin [5,4-b]indol-4-one, which showed an important activity as inhibitors of platelet aggregation, has been evaluated. The compounds studied differed in the physicochemical properties of the substituent occupying the 4' position of the benzilidenamino group. The 4' substituents were: -H, -NO2, -OCH3 and -C6H5. They were tested on V-79 cells, both with and without metabolic activation, and structural chromosome aberrations were scored. Compounds with -H, -NO2 and -OCH3 radicals were active both with and without metabolic activation. Compound with -C6H5 radical was clastogenic only at the highest dose tested and with metabolic activation. It appears that the compound with the biggest and most hydrophobic substituent is the least clastogenic of the series. These results are in agreement with some previous ones obtained in bacteria and show a good correlation between the results of the Ames test and the structural chromosome aberrations test.
García
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Research Centre for Applied Pharmacobiology, University of Navarra, Pamplona, Spain.
Lopez-de-Cerain
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A
Garrido
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E
Gullón
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A
Monge
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A
D001419:Bacteria / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002869:Chromosome Aberrations / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D014227:Triazines / Q000737:chemistry / Q000633:toxicity*
D007211:Indoles; D009153:Mutagens; D014227:Triazines