Synthesis of Novel Azabenzimidazole Bridged bis-Coumarin Compounds, Investigation of Pancreatic Lipase Inhibitory Properties, and Docking Studies

被引：5

作者：

Akyuez, Guelay ^{[1
]}

Faiz, Ozlem ^{[1
]}

Emirik, Mustafa ^{[1
]}

Mentese, Emre ^{[1
]}

机构：

[1] Recep Tayyip Erdogan Univ, Arts & Sci Fac, Dept Chem, TR-53100 Rize, Turkiye

来源：

RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY | 2023年 / 49卷 / SUPPL 1期

关键词：

azabenzimidazole; bis-coumarin; lipase inhibition; docking study; OBESITY;

D O I：

10.1134/S1068162023080083

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this study, new azabenzimidazole-bridged bis-coumarin compounds have been synthesized and screened for their pancreatic lipase inhibitory properties. All compounds showed a considerable lipase inhibitory potential with IC50 values ranging from 0.67 +/- 0.047 to 3.15 +/- 0.081 mu M. Compound N',N''-[(6-bromo-2-oxo-1Himidazo[4,5-b]pyridine-1,3-diyl)bis(1-oxoethane-2,1-diyl)]bis(8-methyl-2-oxo-2H-chromene-3-carbohydrazide) (IIIe) having methoxy group on coumarin ring and compound N',N''-[(6-bromo-2-oxo-1H-imidazo[4,5-b]-pyridine-1,3-diyl)bis(1-oxoethane-2,1-diyl)]bis(6-chloro-2-oxo-2H-chromene-3-carbohydrazide) (IIIb) having -Cl atom on coumarin ring have the highest inhibitory effects. A molecular docking study was performed on the binding pose and affinity of synthesized compounds at the binding sites of lipase.

引用

页码：S96 / S105

页数：10

共 33 条

[1] Synthesis and Docking Studies of Novel Benzimidazole Derivatives Containing Thiophene and Triazole Rings as Potential Urease Inhibitors [J].

Akyuz, G. ;

Emirik, M. ;

Sokmen, B. B. ;

Mentese, E. .

RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY, 2022, 48 (SUPPL 1) :S87-S95

[2]

Alias N., 2017, Adv. Obesity Weight Manag. Control, V6, P163, DOI [10.15406/aowmc.2017.06.00163, DOI 10.15406/AOWMC.2017.06.00163]

[3]

[Anonymous], 2018, Schrodinger Release 2018-4: Desmond Molecular Dynamics System

[4] Design, synthesis, and characterization of some new benzimidazole derivatives and biological evaluation [J].

Bektas, Hakan ;

Sokmen, Bahar B. ;

Aydin, Sinem ;

Mentese, Emre ;

Bektas, Adile ;

Dilekci, Gamze .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 2020, 57 (05) :2234-2242

[5]

Castillo E., 2016, Biocatalysis, V1, P178, DOI [10.1515/boca-2015-0013, DOI 10.1515/BOCA-2015-0013]

[6] Rational Design, Pharmacomodulation, and Synthesis of Dual 5-Hydroxytryptamine 7 (5-HT7)/5-Hydroxytryptamine 2A (5-HT2A) Receptor Antagonists and Evaluation by [18F]-PET Imaging in a Primate Brain [J].

Deau, Emmanuel ;

Robin, Elodie ;

Voinea, Raluca ;

Percina, Nathalie ;

Satala, Grzegorz ;

Finaru, Adriana-Luminita ;

Chartier, Agnes ;

Tamagnan, Gilles ;

Alagille, David ;

Bojarski, Andrzej J. ;

Morisset-Lopez, Severine ;

Suzenet, Franck ;

Guillaumet, Gerald .

JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (20) :8066-8096

[7]

DRENT ML, 1993, INT J OBESITY, V17, P241

[8] OPLS3: A Force Field Providing Broad Coverage of Drug-like Small Molecules and Proteins [J].

Harder, Edward ;

Damm, Wolfgang ;

Maple, Jon ;

Wu, Chuanjie ;

Reboul, Mark ;

Xiang, Jin Yu ;

Wang, Lingle ;

Lupyan, Dmitry ;

Dahlgren, Markus K. ;

Knight, Jennifer L. ;

Kaus, Joseph W. ;

Cerutti, David S. ;

Krilov, Goran ;

Jorgensen, William L. ;

Abel, Robert ;

Friesner, Richard A. .

JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2016, 12 (01) :281-296

[9] Lipase activation by nonionic detergents - The crystal structure of the porcine lipase-colipase-tetraethylene glycol monooctyl ether complex [J].

Hermoso, J ;

Pignol, D ;

Kerfelec, B ;

Crenon, I ;

Chapus, C ;

FontecillaCamps, JC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (30) :18007-18016

[10] Lanthanide-catalyzed cyclocarbonylation and cyclothiocarbonylation: a facile synthesis of benzannulated 1,3-diheteroatom five- and six-membered heterocycles [J].

Jing YuFeng ;

Liu RuiTing ;

Lin YangHui ;

Zhou XiGeng .

SCIENCE CHINA-CHEMISTRY, 2014, 57 (08) :1117-1125

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