N'-亚硝基假木贼碱致癌物代谢活化的研究

Study on metabolism and activation of carcinogens of N'-Nitrosocarbo equates

N'-亚硝基假木贼碱(NAB)是烟草中特异的亚硝胺,被列为第三类可能致癌物。NAB来源于假木贼碱,该化合物本身没有致癌活性,需要经过细胞色素P450酶代谢活化后才具有致癌活性。本文使用简化的Compound I(Cpd I)模型模拟P450酶活性中心,基于密度泛函理论(DFT),对NAB的α-羟基代谢路径进行了理论模拟。结果表明,2'-羟基NAB反应能垒为20.5/18.8 kcal/mol(HS/LS),6'-羟基NAB反应能垒为11.5/13.6 kcal/mol(HS/LS),所以6'-羟基化反应为优势路径。

N’-nitrosoanabasine(NAB)is a specific nitrosamine in tobacco and is classified as the third class of carcinogens.NAB is derived from anabasine.The compound itself has no carcinogenic activity and its metabolites show obvious carcinogenic activity after being activated by cytochrome P450 in vivo.In this paper,a simplified compound I(Cpd I)model was used to simulate the P450 enzymes activity center.Based on the density functional theory(DFT),theα-hydroxyl metabolic pathway of NAB was simulated theoretically.The results showed that the 2’-hydroxylamine NAB has an energy barrier of 20.5/18.8 kcal/mol(HS/LS)and the 6’-hydroxylamine NAB has an energy barrier of 11.5/13.6 kcal/mol(HS/LS),so the 6’-hydroxyl group reaction is the dominant path.