In silico Molecular Docking and ADME Studies of 1,3,4-Thiadiazole Derivatives in Relation to in vitro PON1 Activity

Current Computer-aided Drug Design
Belgin SeverMehlika Dilek Altıntop

Abstract

Paraoxonase 1 (PON1) is a paraoxonase, arylesterase and lactonase associated with protection of lipoproteins and cell membranes against oxidative modification. Based on antioxidative properties of PON1 and significance of 1,3,4-thiadiazoles in pharmaceutical chemistry, herein we aimed to evaluate the potentials of 1,3,4-thiadiazole derivatives as PON1 activators. 2-[[5-(2,4-Difluoro/dichlorophenylamino)-1,3,4-thiadiazol-2-yl]thio]acetophenone derivatives (1-18) were in vitro evaluated for their activator effects on PON1 which was purified using ammonium sulfate precipitation (60-80%) and DEAE-Sephadex anion exchange chromatography. Molecular docking studies were performed for the detection of affinities of all compounds to the active site of PON1. Moreover, Absorption, Distribution, Metabolism and Excretion (ADME) properties of all compounds were also in silico predicted. In silico molecular docking and ADME studies were carried out according to modules of Schrodinger's Maestro molecular modeling package. All compounds, particularly compounds 10, 13 and 17, were determined as promising PON1 activators and apart from compound 1, all of them were detected in the active site of PON1. Besides, ADME results indicated that all compou...Continue Reading

References

Mar 30, 2002·Advanced Drug Delivery Reviews·William L Jorgensen, Erin M Duffy
Apr 21, 2004·Nature Structural & Molecular Biology·Michal HarelDan S Tawfik
Sep 30, 2004·Free Radical Biology & Medicine·Michael Aviram, Mira Rosenblat
Apr 6, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Frédérique RenaultDaniel Rochu
Jul 22, 2008·Clinical Biochemistry·Haci Ahmed AliciSükrü Beydemir
Sep 3, 2008·Biochemical and Biophysical Research Communications·Michal Efrat, Michael Aviram
Jun 25, 2009·Current Opinion in Lipidology·Handrean SoranPaul Durrington
Jul 7, 2009·European Journal of Pharmacology·Deniz Ekinci, Sükrü Beydemir
Mar 27, 2010·Chemico-biological Interactions·C E FurlongC P Zabetian
May 18, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Esra Bayram DilekŞükrü Beydemir
Sep 22, 2012·Journal of Enzyme Inhibition and Medicinal Chemistry·Yusuf AkbabaSükrü Beydemir
Mar 20, 2013·Current Opinion in Lipidology·Michael Aviram, Jacob Vaya
Mar 29, 2014·Journal of Enzyme Inhibition and Medicinal Chemistry·Mehlika Dilek AltintopZafer Asim Kaplancikli
Mar 29, 2014·BMC Veterinary Research·Jose J CeronAsta Tvarijonaviciute
Jan 2, 2015·European Journal of Medicinal Chemistry·Saqlain HaiderHinna Hamid
May 20, 2015·Mini Reviews in Medicinal Chemistry·Joanna Matysiak
Apr 21, 2016·Polish Journal of Veterinary Sciences·M Kulka
May 7, 2016·Current Topics in Medicinal Chemistry·Jaya DwivediSwapnil Sharma
Aug 4, 2016·Anti-cancer Agents in Medicinal Chemistry·Alireza Aliabadi
Mar 18, 2017·Journal of Cheminformatics·George Van Den Driessche, Denis Fourches

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