Research Journal of Pharmacy and Technology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Molecular Docking Studies of N-(((5-Aryl-1,3,4-Oxadiazol-2-yl)Amino)Methyl)- and N-(2,2,2-Trichloro-1-((5-Aryl-1,3,4-Oxadiazol-2-yl)Amino)Ethyl)Carboxamides as Potential Inhibitors of GSK-3β


Affiliations
1 Department of Organic Substances and Pharmaceutical Preparations, Ukrainian State University of Chemical Technology, Gagarin Ave., 8, Dnipro 49005, Ukraine
     

   Subscribe/Renew Journal


In this study it has been carried out in silico modeling of glycogen synthase kinase-3β inhibition by N-amidoalkylated derivatives of 2-amino-1,3,4-oxadiazole, using software ArgusLab 4.0.1. It has been shown that the structures being studied mainly form stronger complexes with the enzyme compared to the known inhibitor. Based on the results of molecular docking, the compounds leaders N-(((5-(2-bromophenyl)-1,3,4-oxadiazol-2-yl)amino)methyl) benzamide and 2,4-dichloro-N-(2,2,2-trichloro-1-((5-(p-tolyl)-1,3,4-oxadiazol-2-yl)amino)ethyl) benzamide have been chosen. The compound N-(((5-(2-bromophenyl)-1,3,4-oxadiazol-2-yl)amino)methyl)benzamide has been known before, and the compound 2,4-dichloro-N-(2,2,2-trichloro-1-((5-(p-tolyl)-1,3,4-oxadiazol-2-yl)amino)ethyl) benzamide has been obtained for the first time. They can be recommended for further studies in the treatment of Alzheimer's disease.

Keywords

Alzheimer’s Disease, 1,3,4-Oxadiazole, Docking, GSK-3β, Inhibitors, Synthesis, ArgusLab.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Hasegawa M. Molecular Mechanisms in the Pathogenesis of Alzheimer's disease and Tauopathies-Prion-Like Seeded Aggregation and Phosphorylation. Biomolecules 2016; 6(2): E24. doi: 10.3390/biom6020024

  • Canter RG, Penney J, Tsai L-H. The road to restoring neural circuits for the treatment of Alzheimer's disease. Nature 2016; 539(7628): 187-196. doi: 10.1038/nature20412

  • Iqbal K, Alonso AC, Chen S, Chohan MO, El-Akkad E, Gong CX, Khatoon S, Li B, Liu F, Rahman A, Tanimukai H, Grundke-Iqbal I. Tau pathology in Alzheimer disease and other tauopathies. Biochim. Biophys. Acta. 2005; 1739(2-3): 198-210. doi: 10.1016/j.bbadis.2004.09.008

  • Chun W, Johnson GV. The role of tau phosphorylation and cleavage in neuronal cell death. Front. Biosci. 2007; 12(2): 733-756. doi: 10.2741/2097

  • Ishiguro K, Takamatsu M, Tomizawa K, Omori A, Takahashi M, Arioka M, Uchida T, Imahori K. Tau protein kinase I converts normal tau protein into A68-like component of paired helical filaments. J. Biol. Chem. 1992; 267(15): 10897-10901.

  • Pei JJ, Tanaka T, Tung YC, Braak E, Iqbal K, Grundke-Iqbal I. Distribution, Levels, and Activity of Glycogen Synthase Kinase-3 in the Alzheimer Disease Brain. J. Neuropathol. Exp. Neurol. 1997; 56(1): 70-78. doi: 10.1097/00005072-199701000-00007

  • Pei JJ, Braak E, Braak H, Grundke-Iqbal I, Iqbal K, Winblad B, Cowburn RF. Distribution of Active Glycogen Synthase Kinase 3β (GSK-3β) in Brains Staged for Alzheimer Disease Neurofibrillary Changes. J. Neuropathol. Exp. Neurol. 1999; 58(9): 1010-1019. doi: 10.1097/00005072-199909000-00011

  • Eldar-Finkelman H, Licht-Murava A, Pietrokovski Sh, Eisenstein M. Substrate Competitive GSK-3 Inhibitors - strategy and Implications. Biochim. Biophys. Acta. 2010; 1804(3): 598-603. doi: 10.1016/j.bbapap.2009.09.010

  • Wagner FF, Bishop JA, Gale JP, Shi X, Walk M, Ketterman J, Patnaik D, Barker D, Walpita D, Campbell AJ, Nguyen Sh, Lewis M, Ross L, Weïwer M, Frank An W, Germain AR, Nag PP, Metkar Sh, Kaya T, Dandapani S, Olson DE, Barbe A-L, Lazzaro F, Sacher JR, Cheah JH, Fei D, Perez J, Munoz B, Palmer M, Stegmaier K, Schreiber SL, Scolnick E, Zhang Y-L, Haggarty SJ, Holson EB, Pan JQ. Inhibitors of Glycogen Synthase Kinase 3 with Exquisite Kinome-Wide Selectivity and Their Functional Effects. ACS Chem. Biol. 2016; 11(7): 1952-1963. doi: 10.1021/acschembio.6b00306

  • Licht-Murava A, Paz R, Vaks L, Plotkin B, Eisenstein M, Eldar-Finkelman H. A unique type of GSK-3 inhibitor brings new opportunities to the clinic. Sci. Signal. 2016; 9(454): ra110. doi: 10.1126/scisignal.aah7102

  • Palomo V, Martinez A. Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015). Expert Opin. Ther. Pat. 2017; 27(6): 657-666. doi: 10.1080/13543776.2017.1259412.

  • Saitoh M, Kunitomo J, Kimura E, Hayase Y, Kobayashi H, Uchiyama N, Kawamoto T, Tanaka T, Mol CD, Dougan DR, Textor GS, Snell GP, Itoh F. Design, synthesis and structure–activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3β. Bioorg. Med. Chem. 2009; 17(5): 2017-2029. doi: 10.1016/j.bmc.2009.01.019

  • Young DC. Computational drug design. New Jersey: John Wiley & Sons, Inc., Hoboken. 2009.

  • Holtje HD, Sippl W, Rognan D, Folkers R. Molecular Modeling. Basic Principles and Applications. Weinheim: Wiley-VCH Verlag GmbH & Co. KGaA; 2008.

  • Zadorozhnii PV, Kiselev VV, Kharchenko AV. Synthesis of Nitrogen-Containing Heterocycles Based on N-(Isothiocyanatoalkyl)carboxamides. In: Novikov V. Ed., Modern Directions in Chemistry, Biology, Pharmacy and Biotechnology. Lviv: Lviv Polytechnic Publishing House; 2015.

  • Zadorozhnii PV, Kiselev VV, Chernous SY, Kharchenko AV, Okhtina OV. Synthesis of amidoalkylation 2-amino-1,3,4-oxadiazole derivatives (In Ukrainian). Vopr Khim Khim Tekhnol. 2012; 6: 30-32.

  • Thompson M. ArgusLab 4.0.1., Planaria software LLC, Seattle, Wash, USA, 2004. (http://www.arguslab.com)

  • Mohammadi-Farani A, Ahmadi A, Nadri H, Aliabadi A. Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects. DARU J. Pharm. Sci. 2013; 21(1): 47. doi: 10.1186/2008-2231-21-47

  • Aliabadi A, Mohammadi-Farani A, Ahmadvand MJ, Rahmani-Khajouei M. Synthesis, docking and acetylcholinesterase inhibitory evaluation of (E)-3-(4-(diethylamino)phenyl)-1-phenylprop-2-en-1-one derivatives with probable anti-Alzheimer effects. J. Rep. Pharm. Sci. 2017; 6(2): 134-141.

  • Mahendran R, Jeyabasker S, Francis A, Manoharan Sh. Insights into the Identification of p38-alpha Mitogen activated Protein Kinase against Pyridazinopyridinone Derivatives in the Treatment of Rheumatoid Arthritis. Res. J. Pharm. Technol. 2017; 10(9): 2875-2879. doi: 10.5958/0974-360X.2017.00507.8

  • Narayanan S, Ramchandran B, Rajendiran S, Chandra S, Tiwari A, Rajarethinam R, Kureeckal VR. Potent antitumour activity of (–)epigallocatechin gallate: indications from in vitro, in vivo and in silico studies. Curr. Sci. 2016; 110(2): 187-195. doi: 10.18520/cs/v110/i2/187-195

  • Ikram H, Bano Kh, Jameel M, Azhar M, Saeed K, Sufian M. Conformational analysis and geometry optimization of apomorphine as an Anti-parkinsonian agent. Pak. J. Pharm. Sci. 2015; 28(5): 1685-1690.

  • Nair NPr, Joy J, Kumar SS, Sathianarayanan S, Manakadan AA, Saranya TS. In-silico docking studies of coumarin derivatives as caspase 8 and PDE4 antagonist. Res. J. Pharm. Technol. 2016; 9(12): 2199-2204. doi:10.5958/0974-360X.2016.00445.5

  • Dash R, Uddin MMN, Hosen SMZ, Rahim ZB, Dinar AM, Kabir MS, Sultan RA, Islam A, Hossain MK. Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer. Bioinformation 2015; 11(12): 543-549. doi: 10.6026/97320630011543

  • Zadorozhnii PV, Kiselev VV, Titova AE, Kharchenko AV, Pokotylo IO, Okhtina OV. Molecular Docking Studies of N-5-Aryl-1,3,4-oxadiazolo-2, 2-dichloroacetamidines as Inhibitors of Enoyl-ACP Reductase Mycobacterium tuberculosis. Res. J. Pharm. Technol. 2017; 10(4), 1091-1097. doi:10.5958/0974-360X.2017.00198.6

  • Zadorozhnii PV, Kiselev VV, Teslenko NO, Kharchenko AV, Pokotylo IO, Okhtina OV, Kryshchyk OV. In Silico Prediction and Molecular Docking Studies of N-Amidoalkylated Derivatives of 1,3,4-Oxadiazole as COX-1 and COX-2 Potential Inhibitors. Res. J. Pharm. Technol. 2017; 10(11): 3957-3963. doi:10.5958/0974-360X.2017.00718.1

  • Muthukumaran P, Rajiniraja M. In silico binding study of bioactive Hispolon and its Analogues to mycobacterial mtfabH. Res. J. Pharm. Technol. 2017, 10(7), 2229-2232. doi:10.5958/0974-360X.2017.00394.8

  • Wang R, Lai L, Wang S. Further development and validation of empirical scoring functions for structure-based binding affinity prediction. J Comput. Aided Mol. Des. 2002; 16(1): 11-26.

  • DeLano WL. The PyMOL Molecular Graphics System, DeLano Scientific: Palo Alto, CA, 2003. (http://www.pymol.org)

  • Pokotylo IO, Zadorozhnii PV, Kiselev VV, Kharchenko AV. Solvent-free synthesis and spectral characteristics of N-(2,2,2-trichloro-1-hydroxyethyl)carboxamides. Chem. Data Collect. 2018; 15-16: 62-66. doi: 10.1016/j.cdc.2018.04.002

  • Guirado A, López-Caracena L, López-Sánchez JI, Sandoval J, Vera M, Bautista D, Gálvez J. A new, high-yield synthesis of 3-aryl-1,2,4-triazoles. Tetrahedron 2016; 72(49): 8055-8060. doi: 10.1016/j.tet.2016.10.045

  • Demydchuk BA, Kondratyuk KM, Kornienko AN, Brovarets VS, Vasylyshyn RYa, Tolmachev AA, Lukin O. A facile synthesis of 1,3-thiazole-4-sulfonyl chlorides. Synth. Commun. 2012; 42(19): 2866-2875. doi: 10.1080/00397911.2011.571356

  • Zadorozhnii PV, Pokotylo IO, Kiselev VV, Kharchenko AV. New 2,2-dichloroacetamidines with heterocyclic fragments. Chem. Sci. Trans. 2016; 5(4): 1056-1062. doi: 10.7598/cst2016.1310 .

  • Zadorozhnii PV, Kiselev VV, Pokotylo IO, Kharchenko AV. A new method for the synthesis of 4H-1,3,5-oxadiazine derivatives. Heterocycl. Commun. 2017; 23(5): 369-374. doi: 10.1515/hc-2017-0083

  • Zadorozhnii PV, Kiselev VV, Pokotylo IO, Okhtina OV., Kharchenko AV. Synthesis and mass spectrometric fragmentation pattern of 6-(4-chlorophenyl)-N-aryl-4-(trichloromethyl)-4H-1,3,5-oxadiazin-2-amines. Heterocycl. Commun. 2018; 24(5): 273-278. doi: 10.1515/hc-2018-0082

  • Zadorozhnii P, Kiselev V, Krvavych A, Novikov V, Kharchenko A. The molecular structure N-{2,2,2-trichloro-1-[(5-phenyl-1,3,4-thiadiazol-2-yl)amino]ethyl}acet- and Thioacetamide. Res. J. Pharm., Biol. Chem. Sci. 2015; 6(2): 689-695.

  • Drach BS, Brovarets VS, Smolii OB. Syntheses of Nitrogen-Containing Compounds On the Basis of Amidoalkylation Agents. Naukova Dumka, Kiev, 1992.

  • Larocca JP, Leonard JM, Weaver WE. The preparation and fungicidal activity of some amides of chloral and α,α,β-trichlorobutyraldehyde. J. Org. Chem. 1951; 16(1): 47-50. doi: 10.1021/jo01141a007

  • Hudson HR, Mavrommatis ChN, Pianka M. Organophosphorus compounds as potential fungicides. Part V. The preparation and properties of some novel N,N,N’,N’-tetramethyl-N”-(1-substituted-2,2,2-trichloroethyl)phosphoric triamide. Phosphorus Sulfur Silicon Relat. Elem. 1996; 108(1-4): 141-153. doi: 10.1080/10426509608029647

  • Podgornova VA, Farafontova VI, Borovkova GV, Ustavshchikov BF. Synthesis of N-substituted acrylamides. Part 2. Synthesis and use of N-(1-hydroxy-2,2,2-trichloroethyl)acryl- and -methacrylamide, new vulcanizing agents for rubbers. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 1999; 42: 58-61.

  • Aizina JA, Rozentsveig I.B, Levkovskaya GG. A novel synthesis of chloroacetamide derivatives via C-amidoalkylation of aromatics by 2-chloro-N-(2,2,2-trichloro-1-hydroxyethyl)acetamide, Arkivoc 2011; 8: 192-199. doi: 10.3998/ark.5550190.0012.815 .

  • Altenbach RJ, Bai H, Brioni JD, Carroll WA, Gopalakrishnan M, Gregg RJ, Holladay MW, Huang PP, Kincaid JF, Kort ME, Kym PhR, Lynch JK, Perez-Medrano A, Zhang H.Q. Potassium channel openers. U.S. Patent No. 2002/28836 A1, 2002; Chem. Abstr. 2002; 136: 231935.

  • Schraufstaetter E, Goennert R. Alkyliden- und Aryliden-bis-chloracetamide, eine neue Gruppe gegen Bilharziose wirksamer Verbindungen. Z. Naturforsch. B. 1962; 17(8): 505-516. doi: 10.1515/znb-1962-0804

  • Zadorozhnii PV, Kiselev VV, Pokotylo IO, Okhtina OV, Kharchenko AV. In silico prediction of anticonvulsant activity of N-(2,2,2-trichloro-1-hydroxyethyl)carboxamides. J. Chem. Pharm. Sci. 2017; 10(3): 1099-1105.

  • Zadorozhnii PV, Popykhach NP, Kiselev VV, Pokotylo IO, Okhtina OV, Kharchenko A.V. In Silico Prediction of Anticonvulsant Activity of N-(2,2,2-Trichloro-1-hydroxyethyl)alkenyl- and –alkylarylcarboxamides. Res. J. Pharm. Technol. 2018; 11(2): 711-716. doi:10.5958/0974-360X.2018.00134.8

  • Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Sheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J. A Selective Inhibitor of eIF2alpha Dephosphorylation Protects Cells from ER Stress, Science 2005; 307 (5711): 935-939. doi: 10.1126/science.1101902

  • Liu J, He K-L, Li X. SAR, cardiac myocytes protection activity and 3D-QSAR studies of salubrinal and its potent derivatives. Curr. Med. Chem. 2012; 19(35): 6072-6079. doi: 10.2174/0929867311209066072

  • Long K, Boyce M, Lin H, Yuan J, Ma D. Structure-activity relationship studies of salubrinal lead to its active biotinylated derivative. Bioorg. Med. Chem. Lett. 2005; 15(17): 3849-3852. doi: 10.1016/j.bmcl.2005.05.120

  • Nakanishi J. Infrared absorption spectroscopy. Holden-Day Inc., San Francisco, 1962.


Abstract Views: 209

PDF Views: 0




  • Molecular Docking Studies of N-(((5-Aryl-1,3,4-Oxadiazol-2-yl)Amino)Methyl)- and N-(2,2,2-Trichloro-1-((5-Aryl-1,3,4-Oxadiazol-2-yl)Amino)Ethyl)Carboxamides as Potential Inhibitors of GSK-3β

Abstract Views: 209  |  PDF Views: 0

Authors

Pavlo V. Zadorozhnii
Department of Organic Substances and Pharmaceutical Preparations, Ukrainian State University of Chemical Technology, Gagarin Ave., 8, Dnipro 49005, Ukraine
Ihor O. Pokotylo
Department of Organic Substances and Pharmaceutical Preparations, Ukrainian State University of Chemical Technology, Gagarin Ave., 8, Dnipro 49005, Ukraine
Vadym V. Kiselev
Department of Organic Substances and Pharmaceutical Preparations, Ukrainian State University of Chemical Technology, Gagarin Ave., 8, Dnipro 49005, Ukraine
Oxana V. Okhtina
Department of Organic Substances and Pharmaceutical Preparations, Ukrainian State University of Chemical Technology, Gagarin Ave., 8, Dnipro 49005, Ukraine
Aleksandr V. Kharchenko
Department of Organic Substances and Pharmaceutical Preparations, Ukrainian State University of Chemical Technology, Gagarin Ave., 8, Dnipro 49005, Ukraine

Abstract


In this study it has been carried out in silico modeling of glycogen synthase kinase-3β inhibition by N-amidoalkylated derivatives of 2-amino-1,3,4-oxadiazole, using software ArgusLab 4.0.1. It has been shown that the structures being studied mainly form stronger complexes with the enzyme compared to the known inhibitor. Based on the results of molecular docking, the compounds leaders N-(((5-(2-bromophenyl)-1,3,4-oxadiazol-2-yl)amino)methyl) benzamide and 2,4-dichloro-N-(2,2,2-trichloro-1-((5-(p-tolyl)-1,3,4-oxadiazol-2-yl)amino)ethyl) benzamide have been chosen. The compound N-(((5-(2-bromophenyl)-1,3,4-oxadiazol-2-yl)amino)methyl)benzamide has been known before, and the compound 2,4-dichloro-N-(2,2,2-trichloro-1-((5-(p-tolyl)-1,3,4-oxadiazol-2-yl)amino)ethyl) benzamide has been obtained for the first time. They can be recommended for further studies in the treatment of Alzheimer's disease.

Keywords


Alzheimer’s Disease, 1,3,4-Oxadiazole, Docking, GSK-3β, Inhibitors, Synthesis, ArgusLab.

References