In this study, the mutagenicity of the anti-inflammatory parsalmide [5-amino-N-butyl-2-(2-propynyloxy)-benzamide] analogues PA7 [5-amino-N-butyl-2-cyclohexyloxy-benzamide], PA10 [5-amino-N-butyl-2-phenoxy-benzamide] and PA31 [5-amino-N-butyl-2-(p-tolyloxy)-benzamide] was determined by an Ames Salmonella assay. The experiments were performed by preincubating the compounds in the absence and presence of a post-mitochondrial fraction (S9) of rat liver homogenate from phenobarbital/beta-naphtoflavone treated rats. No mutagenic effect was observed after direct testing (no S9 added) in Salmonella typhymurium strains TA98, TA100, TA102, TA1535 and TA1537. However, in the presence of S9, the test substances triggered mutagenic responses in strains TA100 and TA98. PA31 presented the strongest mutagenic potential. The reversion rates in the presence of PA31 were about 2-19 fold higher than spontaneous mutation rates. In the presence of PA7, the reversion increased 2-14-fold over spontaneous rates. While PA10 showed a relatively mild mutagenic potential, as the number of revertants did not exceed 2.5 times the number of spontaneous mutations. Mass spectrometric analysis of the in vitro biotransformation showed that S9 converted (%), regioselectively, PA7 (19%), PA10 (7%) and PA31 (12%) into hydroxy-derivatives.

中文翻译：

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通过生物转化为羟基衍生物触发的抗炎性帕拉米胺类似物PA7，PA10和PA31的体外诱变性。

在这项研究中，抗炎性杀虫药[5-氨基-N-丁基-2-（2-丙炔氧基）-苯甲酰胺]类似物PA7 [5-氨基-N-丁基-2-环己氧基-苯甲酰胺]，PA10的致突变性通过Ames沙门氏菌测定法测定[5-氨基-N-丁基-2-苯氧基-苯甲酰胺]和PA31 [5-氨基-N-丁基-2-（对甲苯氧基）-苯甲酰胺]。通过在不存在和存在来自苯巴比妥/β-萘黄酮处理的大鼠的大鼠肝匀浆的线粒体后级分（S9）存在下预孵育化合物来进行实验。在鼠伤寒沙门氏菌菌株TA98，TA100，TA102，TA1535和TA1537直接测试（未添加S9）后，未观察到诱变作用。然而，在存在S9的情况下，测试物质在菌株TA100和TA98中触发了诱变反应。PA31具有最强的诱变潜力。在存在PA31的情况下，回复率比自发突变率高约2-19倍。在存在PA7的情况下，逆转率比自发率提高了2-14倍。虽然PA10表现出相对温和的诱变潜力，但其回复子的数量不超过自发突变数的2.5倍。体外生物转化的质谱分析表明，S9在区域选择性地将PA7（19％），PA10（7％）和PA31（12％）区域转化为羟基衍生物。