بررسی نحوه اتصال 9-هیدروکسی آریستولوکیک اسید، دیکلوفناک و ایندومتاسین به آنزیم فسفولیپاز A2

ابراهیمی, محسن and فیروزی, امیدرضا and میری, رامین and رزاقی اصل, نیما and عبادی, احمد (1397) بررسی نحوه اتصال 9-هیدروکسی آریستولوکیک اسید، دیکلوفناک و ایندومتاسین به آنزیم فسفولیپاز A2. Interdisciplinary Sciences: Computational Life Sciences ــ 10 (2). pp. 400-410. شاپا 1913-2751

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Official URL: https://link.springer.com/article/10.1007/s12539-0...


Structural insight into binding mode of 9-hydroxy Aristolochic acid, diclofenac and indomethacin to PLA2

English Abstract

Phospholipase A2 (PLA2) catalyzes the hydrolysis of phospholipids into arachidonic acid and lysophospholipids. Arachidonic acid is modified by cyclooxygenases into active compounds called eicosanoids that act as signaling molecules in a number of physiological processes. Excessive production of eicosanoids leads to several pathological conditions such as inflammation. In order to block the inflammatory effect of these compounds, upstream enzymes such as PLA2 are valid targets. In the present contribution, molecular dynamic analysis was performed to evaluate the binding of diclofenac, 9-hydroxy aristolochic acid (9-HAA) and indomethacin to PLA2. Obtained results revealed that 9-HAA could form a more stable complex with PLA2 when compared to diclofenac and indomethacin. Furthermore, analysis of intermolecular binding energy components indicated that hydrophobic interactions were dominant in binding process. On the basis of obtained data, inhibitors bearing fused rings with hydrogen acceptor/donor substituent(s) interacted with His48 and Asp49 residues of the active site. More affinity toward PLA2 might be envisaged through negatively charged moieties via interaction with Trp31, Lys34 and Lys69.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :محسن ابراهیمی
نویسنده :امیدرضا فیروزی
نویسنده :رامین میری
نویسنده مسئول :نیما رزاقی اصل
نویسنده مسئول :احمد عبادی
Additional Information:IF: 1.418 Indexed in: ISI, PubMed/Medline/Index Medicus, Scopus, EMBASE
کلیدواژه ها (انگلیسی):Phospholipase A2 , Inflammation , In silico drug design , Molecular dynamic simulation
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
QV pharmacology
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:8442
Deposited By: Mrs sepideh Dashti
Deposited On:03 Nov 1395 06:10
Last Modified:05 Dec 1400 08:28

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