Bullion K, Ohnishi S, Osawa Y
Endocrine Biochemistry Department, Medical Foundation of Buffalo Research Institute, NY 14203.
Endocr Res. 1991;17(3-4):409-19. doi: 10.3109/07435809109106817.
In a study of the effect of N-n-octanoylnornicotine and other acyl derivatives of nornicotine on the aromatization of androstenedione by human placental microsomal aromatase, we found that N-n-octanoylnornicotine, a component of cigarette smoke, exhibited competitive inhibition with an apparent Ki of 0.65 microM. This is comparable to that of aminoglutethimide, the clinically-used non-steroidal aromatase inhibitor. N-n-Decanoylnornicotine and N-(4-hydroxyundecanoyl)nornicotine exhibited apparent Ki values of 0.86 microM and 0.24 microM, respectively. This study suggests that cigarette smoke components may have a direct effect on estrogen biosynthesis and that these compounds may prove to be useful parent structures for development of active site probes for further elucidation of estrogen biosynthesis and might eventually lead to the development of alternative non-steroidal anti-cancer therapy.
在一项关于N-正辛酰去甲烟碱及其他去甲烟碱酰基衍生物对人胎盘微粒体芳香化酶催化雄烯二酮芳香化作用影响的研究中，我们发现香烟烟雾成分N-正辛酰去甲烟碱表现出竞争性抑制作用，其表观抑制常数Ki为0.65微摩尔，这与临床使用的非甾体芳香化酶抑制剂氨鲁米特相当。N-正癸酰去甲烟碱和N-（4-羟基十一酰基）去甲烟碱的表观Ki值分别为0.86微摩尔和0.24微摩尔。该研究表明，香烟烟雾成分可能对雌激素生物合成有直接影响，这些化合物可能被证明是开发活性位点探针的有用母体结构，以进一步阐明雌激素生物合成，最终可能会导致替代非甾体抗癌疗法的开发。
