چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| Background Aldehyde oxidase (AOX) is an important molybdenum-containing enzyme with high similarity with xanthine oxidase (XO). AOX involved in the metabolism of a large array of aldehydes and N-heterocyclic compounds and its activity is highly substrate-dependent. Objectives The aim of this work was to study the effect of five important phenothiazine drugs on AOX activity using benzaldehyde and phenanthridine as aldehyde and N-heterocyclic substrates, respectively. Methods The effect of trifluperazine, chlorpromazine, perphenazine, thioridazine and promethazine on rat liver AOX was measured spectrophotometrically. To predict the mode of interactions between the studied compounds and AOX, a combination of homology modeling and a molecular docking study was performed. Results All phenothiazines could inhibit AOX activity measured either by phenanthridine or benzaldehyde with almost no effect on XO activity. In the case of benzaldehyde oxidation, the lowest and highest half-maximal inhibitory concentration ( IC50) values were obtained for promethazine ( IC50 = 0.9 μM), and trifluoperazine ( IC50 = 3.9 μM), respectively; whereas perphenazine ( IC50 = 4.3 μM), and trifluoperazine ( IC50 = 49.6 μM) showed the strongest and weakest inhibitory activity against AOX-catalyzed phenanthridine oxidation, respectively. The in silico findings revealed that the binding site of thioridazine is near the dimer interference, and that hydrophobic interactions are of great importance in all the tested phenothiazines. Conclusion The five studied phenothiazine drugs showed dual inhibitory effects on AOX activity towards aldehydes and N-heterocycles as two major classes of enzyme substrates. Most of the interactions between the phenothiazine-related drugs and AOX in the binding pocket showed a hydrophobic nature. |
| نویسنده | نفر چندم مقاله |
|---|---|
| محمدرضا رشیدی شاهگلی | هفتم |
| سیاوش دستمالچی | سوم |
| مریم حمزه میوه رود | چهارم |
| فرناز دریس عبداله پور | اول |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| European Journal of Drug Metabolism and Pharmacokinetics Volume issue 2018 [doi 10.1007_s13318-018-0514-6] Abdolahpour, Farnaz Deris; Sadegh, Lida Abolaliporan; Dastmalchi -- Effects of Pheno.pdf | 1398/01/17 | 2417291 | دانلود |
