Debnath A K, Debnath G, Shusterman A J, Hansch C
Department of Chemistry, Pomona College, Claremont, California 91711.
Environ Mol Mutagen. 1992;19(1):37-52. doi: 10.1002/em.2850190107.
Quantitative structure-activity relationships (QSAR) have been derived for the mutagenic activity of 88 aromatic and heteroaromatic amines acting on Salmonella typhimurium TA98 + S9 and 67 amines acting on TA100 + S9. Mutagenic activity is linearly dependent on hydrophobicity, the energy of the highest occupied molecular orbital, and the energy of the lowest unoccupied molecular orbital of the amine. The dependence of mutagenic activity on hydrophobicity and electronic effects is nearly identical for TA98 and TA100. Mutagenic activity in TA98 is also found to depend on the size of the aromatic ring system. Different QSARs are derived for the mutagenic activity of hydrophilic amines (log P less than 1) acting on either TA98 or TA100. The mechanism of amine activation and reaction with DNA is considered in light of these findings.
已经得出了88种作用于鼠伤寒沙门氏菌TA98 + S9的芳香族和杂芳香族胺以及67种作用于TA100 + S9的胺的致突变活性的定量构效关系（QSAR）。致突变活性与胺的疏水性、最高占据分子轨道的能量以及最低未占据分子轨道的能量呈线性相关。对于TA98和TA100，致突变活性对疏水性和电子效应的依赖性几乎相同。还发现TA98中的致突变活性取决于芳香环系统的大小。针对作用于TA98或TA100的亲水性胺（log P小于1）的致突变活性得出了不同的QSAR。根据这些发现，对胺的活化机制以及与DNA的反应进行了探讨。
