通过抑制PDE9筛选穿心莲抗糖尿病次生代谢物。

IF 2.1 Q3 CHEMISTRY, MEDICINAL
Netty Ino Ischak, La Ode Aman, Hamsidar Hasan, Akram La Kilo, Aiyi Asnawi
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引用次数: 3

摘要

背景与目的:穿心莲(Andrographis paniculata, AP)作为一种抗糖尿病药物已被广泛应用,但其抗糖尿病作用的机制和活性物质,特别是其抑制靶点之一磷酸二酯酶-9 (PDE9)的作用尚未见报道。本研究的目的是通过抑制PDE9从AP的次级代谢物化合物中鉴定出新的抗糖尿病候选物。实验方法:为了制备AP和PDE9次级代谢物的化学结构,使用Discovery Studio Visualizer、AutoDockTools、AutoDock和Gromacs以及其他一些支持软件包进行对接和分子动力学模拟。结果:分子对接模拟结果表明,AP 46个次级代谢产物中C00003672 (-11.35 kcal/mol)和C00041378 (-9.27 kcal/mol)的结合自由能高于天然配体(-9.23 kcal/mol)。分子动力学结果表明,化合物C00041378与PDE9的两个活性侧残基TRY484和PHE516相互作用。PDE9与C00003672、C00041378和49E的相互作用ΔGMMGBSA分别为51.69、-56.43和-48.13 kcal/mol, PDE9与C00003672、C00041378和49E的相互作用ΔGMMPBSA分别为-12.26、-16.24和-11.79 kcal/mol。结论与意义:基于对接和分子动力学模拟对AP次级代谢产物的评价,提示C00041378化合物可能通过抑制PDE9成为抗糖尿病候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

<i>In silico</i> screening of <i>Andrographis paniculata</i> secondary metabolites as anti-diabetes mellitus through PDE9 inhibition.

<i>In silico</i> screening of <i>Andrographis paniculata</i> secondary metabolites as anti-diabetes mellitus through PDE9 inhibition.

<i>In silico</i> screening of <i>Andrographis paniculata</i> secondary metabolites as anti-diabetes mellitus through PDE9 inhibition.

In silico screening of Andrographis paniculata secondary metabolites as anti-diabetes mellitus through PDE9 inhibition.

Background and purpose: Andrographis paniculata (AP) has long been used as an anti-diabetic agent, but the mechanism of action and active substance responsible for the anti-diabetic effect, particularly by inhibiting phosphodiesterase-9 (PDE9), which is one of the targets of anti-diabetic medications, have not been reported. The aim of the present study was to identify a new anti-diabetes candidate from secondary metabolite compounds of AP through PDE9 inhibition.

Experimental approach: In order to prepare the chemical structures of the secondary metabolites of AP and PDE9, docking and molecular dynamics simulations were run using Discovery Studio Visualizer, AutoDockTools, AutoDock, and Gromacs, along with a few other supporting software packages.

Findings/results: Molecular docking simulations showed that two of the 46 secondary metabolites of AP had higher free energies of binding, C00003672 (-11.35 kcal/mol) and C00041378 (-9.27 kcal/mol), than native ligand (-9.23 kcal/mol). The results of molecular dynamics showed that compound C00041378 interacted with TRY484 and PHE516, two active side residues of PDE9. ΔGMMGBSA interactions of PDE9 with C00003672, C00041378, and 49E compounds are 51.69, -56.43, and -48.13 kcal/mol, respectively, as well as ΔGMMPBSA interactions of PDE9 with C00003672, C00041378, and 49E compounds, were -12.26, -16.24, and -11.79 kcal/mol kcal/mol, respectively.

Conclusions and implications: Based on the evaluations of AP secondary metabolites using docking and molecular dynamics simulation, it is suggested that the C00041378 compound has the potential to be an antidiabetic candidate by inhibiting PDE9.

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来源期刊
Research in Pharmaceutical Sciences
Research in Pharmaceutical Sciences CHEMISTRY, MEDICINAL-
CiteScore
3.60
自引率
19.00%
发文量
50
审稿时长
34 weeks
期刊介绍: Research in Pharmaceutical Sciences (RPS) is included in Thomson Reuters ESCI Web of Science (searchable at WoS master journal list), indexed with PubMed and PubMed Central and abstracted in the Elsevier Bibliographic Databases. Databases include Scopus, EMBASE, EMCare, EMBiology and Elsevier BIOBASE. It is also indexed in several specialized databases including Scientific Information Database (SID), Google Scholar, Iran Medex, Magiran, Index Copernicus (IC) and Islamic World Science Citation Center (ISC).
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