Design, Synthesis, and Biological Studies of Flavone-Based Esters and Acids as Potential P450 2A6 Inhibitors.
Design, Synthesis, and Biological Studies of Flavone-Based Esters and Acids as Potential P450 2A6 Inhibitors.
复制标题
DOI：
10.1021/acs.chemrestox.3c00249
复制
发表时间：
2023-12-18
影响因子：
4.1
通讯作者：
Foroozesh, Maryam
中科院分区：
文献类型：
--
作者：
Goyal, Navneet;Do, Camilla;Sridhar, Jayalakshmi;Shaik, Shahensha;Thompson, Anthony;Perry, Timothy;Carter, Loren;Foroozesh, Maryam
本研究旨在探讨P450 2A6对尼古丁代谢的抑制作用，作为戒烟从而预防吸烟相关疾病和死亡的潜在手段。吸烟是许多疾病和残疾的主要原因，几乎损害了身体的每一个器官。根据疾病控制和预防中心(CDC)的报告，超过1600万美国人患有由吸烟引起的疾病。平均而言，吸烟者的预期寿命比不吸烟者少约10年。戒烟可以大大降低吸烟相关疾病的发病率，包括癌症。在7000多种香烟烟雾成分中，至少有70种是已知的致癌物质，包括多环芳烃、N-亚硝胺和芳香胺。尼古丁是一种对烟草的成瘾和精神药理作用负责的化合物。细胞色素P450酶负责许多烟草成分的I相代谢，包括尼古丁。尼古丁主要由细胞色素P450、2A6和2A13代谢成可替宁。这种新陈代谢减少了血液中可用尼古丁的数量，导致吸烟行为增加，从而暴露在烟草毒物和致癌物中。在这里，我们报道了一些新的基于黄酮类的酯和酸的合成和P450 2A6抑制活性。所研究的三种黄酮衍生物被发现是该酶的强有力的竞争性抑制剂。对接研究被用来确定这些抑制剂活性的可能机制。
As a potential means for smoking cessation and consequently prevention of smoking-related diseases and mortality, in this study, our goal was to investigate the inhibition of nicotine metabolism by P450 2A6. Smoking is the main cause of many diseases and disabilities and harms nearly every organ of the body. As reported by the Centers for Disease Control and Prevention (CDC), more than 16 million Americans are living with diseases caused by smoking. On average, the life expectancy of a smoker is about 10 years less than a nonsmoker. Smoking cessation can substantially reduce the incidence of smoking-related diseases, including cancer. At least, 70 of the more than 7000 cigarette smoke components, including polycyclic aromatic hydrocarbons, N-nitrosamines, and aromatic amines, are known carcinogens. Nicotine is the compound responsible for the addictive and psychopharmacological effects of tobacco. Cytochrome P450 enzymes are responsible for the phase I metabolism of many tobacco components, including nicotine. Nicotine is mainly metabolized by cytochrome P450s 2A6 and 2A13 to cotinine. This metabolism decreases the amount of available nicotine in the bloodstream, leading to increased smoking behavior and thus exposure to tobacco toxicants and carcinogens. Here, we report the syntheses and P450 2A6 inhibitory activities of a number of new flavone-based esters and acids. Three of the flavone derivatives studied were found to be potent competitive inhibitors of the enzyme. Docking studies were used to determine the possible mechanisms of the activity of these inhibitors.
登录
查看更多内容
影响因子：
3.9
作者：
Bao, ZP;He, XY;Hong, JY
通讯作者：
Hong, JY
DOI：
10.1007/bf03189632
发表时间：
1982-01-01
影响因子：
1.9
作者：
GORROD, JW;HIBBERD, AR
通讯作者：
HIBBERD, AR
影响因子：
7.3
作者：
PETERSON, LA;TREVOR, A;CASTAGNOLI, N
通讯作者：
CASTAGNOLI, N
DOI：
10.1080/00498254.2021.1950866
发表时间：
2021-09
期刊：
Xenobiotica; the fate of foreign compounds in biological systems
影响因子：
--
作者：
Nagayoshi H;Murayama N;Takenaka S;Kim V;Kim D;Komori M;Yamazaki H;Guengerich FP;Shimada T
通讯作者：
Shimada T
影响因子：
4.1
作者：
Foroozesh, M;Primrose, G;Guengerich, FP
通讯作者：
Guengerich, FP