School of Pharmacy, University of Eastern Finland, POB 1627, 70211 Kuopio, Finland.
Bioorg Med Chem. 2011 Dec 1;19(23):7186-93. doi: 10.1016/j.bmc.2011.09.054. Epub 2011 Oct 4.
The human CYP2A6 enzyme metabolises several xenobiotics including nicotine, the addictive component in tobacco. Reduced activity of CYP2A6, either for genetic reasons or by administering inhibitors of CYP2A6, reduces tobacco smoking. The aim was to design novel inhibitors of CYP2A6 using 3D-QSAR analysis combined with virtual screening. A 3D-QSAR model was utilised to identify the most important features of the inhibitors, and this knowledge was used to design inhibitors for CYP2A6. Chemical database screening yielded several potent inhibitor candidates such as alkylamine derivatives (compound no. 5, IC(50)=0.1 μM) and 1-benzothiophene-3-carbaldehyde that can be used as lead compounds in the development of drugs for smoking reduction therapy.
人类 CYP2A6 酶代谢多种外源物质，包括尼古丁，烟草中的成瘾成分。CYP2A6 活性降低，无论是由于遗传原因还是通过给予 CYP2A6 抑制剂，都会减少吸烟。目的是使用 3D-QSAR 分析结合虚拟筛选来设计新型 CYP2A6 抑制剂。使用 3D-QSAR 模型来确定抑制剂的最重要特征，并且利用这些知识来设计 CYP2A6 的抑制剂。化学数据库筛选产生了几种有效的抑制剂候选物，如烷基胺衍生物（化合物 5，IC50=0.1 μM）和 1-苯并噻吩-3-甲醛，它们可作为减少吸烟治疗药物开发的先导化合物。
