Copyright (c) 2016 AJC
This work is licensed under a Creative Commons Attribution 4.0 International License.
Synthesis, Spectral Characterization and Molecular Docking Studies of Lawsone Derivatives as Protein Kinase Inhibitors
Corresponding Author(s) : P.R. Kavitha Rani
Asian Journal of Chemistry,
Vol. 28 No. 12 (2016): Vol 28 Issue 12
Abstract
Naphthaquinone moiety is present in various cancer drugs. We have synthesized two derivatives from lawsone using phenylenediamine and 4-amino phenol by ultra sound irradiation technique. The synthesized derivatives 10,12-dihydro-5-10-diazatetraphene-12-one and 2-(4-anilino)-1,4-naphthaquinone were characterized by elemental analysis and various spectral techniques like UV-visible, IR, NMR (1H and 13C) and gas chromatographic mass spectra. The study focus to predict the anticancer activity of the synthesized compounds by in silico molecular docking studies using Schrödinger software suit. The selected protein was protein kinase CK2 (PDB ID: 1M2R). Both the derivatives have better interaction with various amino acids present in active site of the protein than the parent compound lawsone. The new derivative 2-(4-anilino)-1,4-naphthaquinone exhibit lowest glide score of -2.8 kcal/mol. From the result, structural modification of the parent compound proved to be a lead compound for further drug design investigations.
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References
R.P. Verma, Anticancer Agents Med. Chem., 6, 489 (2006); doi:10.2174/187152006778226512#sthash.gDYL223T.dpuf.
A.P. Neves, M.X.G. Pereira, E.J. Peterson, R. Kipping, M.D. Vargas, F.P. Silva Jr., J.W.M. Carneiro and N.P. Farrell, J. Inorg. Biochem., 119, 54 (2013); doi:10.1016/j.jinorgbio.2012.10.007.
H. Nohl, W. Jordan and R.J. Youngman, Adv. Free Radic. Biol. Med., 2, 211 (1986); doi:10.1016/S8755-9668(86)80030-8.
G.H. Mahdavinia, M. Mirzazadeh and B. Notash, Tetrahedron Lett., 54, 3487 (2013); doi:10.1016/j.tetlet.2013.04.082.
S. van Aeken, J. Deblander, J. De Houwer, T. Mosselmans and K. Abbaspour-Tehrani, Tetrahedron, 67, 512 (2011); doi:10.1016/j.tet.2010.10.082.
J.J. Ha, C.W. Jeon, P. Kang, I. Kang, S.Y. Nam and Y.-H. Kim, Synth. Met., 180, 32 (2013); doi:10.1016/j.synthmet.2013.07.012.
E. De Moliner, S. Moro, S. Sarno, G. Zagotto, G. Zanotti, L.A. Pinna and R. Battistutta, J. Biol. Chem., 278, 1831 (2003);doi:10.1074/jbc.M209367200.
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A. Weisseberger and E.S. Prabanker, Organic Solvents Physical Properties and Methods of Purification, Interscience, New York (1963).
P.R. Kavitha Rani, A. Fernandez, A. George, V.K. Remadevi, M.R. Sudarsanakumar, S.P. Laila and M. Arif, Spectrochim. Acta A, 135, 1156 (2015); doi:10.1016/j.saa.2014.07.092.
J.L. Bolton, M.A. Trush, T.M. Penning, G. Dryhurst and T.J. Monks, Chem. Res. Toxicol., 13, 135 (2000); doi:10.1021/tx9902082.
H. Nohl, W. Jordan and R.J. Youngman, Adv. Free Radic. Biol. Med., 2, 211 (1986); doi:10.1016/S8755-9668(86)80030-8.
D.K. Waiker, C. Karthikeyan, V. Poongavanam, J. Kongsted, O. Lozach, L. Meijer and P. Trivedi, Bioorg. Med. Chem., 22, 1909 (2014); doi:10.1016/j.bmc.2014.01.044.
R.M. Silverstein, G.C. Basseler and C. Morill, Spectrometric Identification of organic Compounds, Wiley, New York (2003).
K. Niefind, J. Raaf and O.-G. Issinger, Cell. Mol. Life Sci., 66, 1800 (2009); doi:10.1007/s00018-009-9149-8.
S. Sarno and L.A. Pinna, Mol. Biosyst., 4, 889 (2008); doi:10.1039/B805534C.
R. Battistutta, M. Mazzorana, S. Sarno, Z. Kazimierczuk, G. Zanotti and L.A. Pinna, Chem. Biol., 12, 1211 (2005); doi:10.1016/j.chembiol.2005.08.015.