Generic placeholder image

Letters in Organic Chemistry

Author(s): Agnieszka A. Kaczor*, Karolina Wojtunik-Kulesza, Tomasz M. Wróbel, Dariusz Matosiuk and Monika Pitucha

DOI: 10.2174/1570178618666210119121438

DownloadDownload PDF Flyer Cite As
5-Methoxy-1-methyl-2-{[4-(2-hydroxyphenyl)piperazin-1-yl]methyl}-1Hindole (KAD22) with Antioxidant Activity

Page: [263 - 275] Pages: 13

  • * (Excluding Mailing and Handling)

Abstract

Compound KAD22 (5-methoxy-1-methyl-2-{[4-(2-hydroxyphenyl)piperazin-1-yl]methyl}- 1H-indole) was designed as a potential dopamine D2 receptor agonist with antioxidant activity for possible treatment of Parkinson’s disease. The compound was obtained from 5-methoxy-1-methyl-1H-indole- 2-carbaldehyde and 2-(piperazin-1-yl)phenol. KAD22 showed no affinity to dopamine D2 receptor but it is a potent antioxidant. Experimental and computational structural studies (conformational analysis, HOMO and LUMO orbitals, electrostatic potential map, non-covalent interaction plot, spectral properties, ligand-receptor interactions) of KAD22 were performed to address its biological activity.

Keywords: Antioxidant activity, dopamine receptors, indole derivatives, molecular modeling, Parkinson’s disease, structural studies.

Graphical Abstract

[1]
Tysnes, O-B.; Storstein, A. J. Neural Transm. (Vienna), 2017, 124(8), 901-905.
[http://dx.doi.org/10.1007/s00702-017-1686-y] [PMID: 28150045]
[2]
Andlin-Sobocki, P.; Jönsson, B.; Wittchen, H-U.; Olesen, J. Eur. J. Neurol., 2005, 12(Suppl. 1), 1-27.
[http://dx.doi.org/10.1111/j.1468-1331.2005.01202.x] [PMID: 15877774]
[3]
Armstrong, M.J.; Okun, M.S. JAMA, 2020, 323(6), 548-560.
[http://dx.doi.org/10.1001/jama.2019.22360] [PMID: 32044947]
[4]
Vijverman, A-C.; Fox, S.H. Expert Rev. Clin. Pharmacol., 2014, 7(6), 761-777.
[http://dx.doi.org/10.1586/17512433.2014.966812] [PMID: 25318835]
[5]
Wilson, H.; Pagano, G.; de Natale, E.R.; Mansur, A.; Caminiti, S.P.; Polychronis, S.; Middleton, L.T.; Price, G.; Schmidt, K.F.; Gunn, R.N.; Rabiner, E.A.; Politis, M. Mov. Disord., 2020, 35(8), 1416-1427.
[http://dx.doi.org/10.1002/mds.28064] [PMID: 32347983]
[6]
Papa, S.; De Rasmo, D. Trends Mol. Med., 2013, 19(1), 61-69.
[http://dx.doi.org/10.1016/j.molmed.2012.11.005] [PMID: 23265841]
[7]
Reynolds, A.; Laurie, C.; Mosley, R.L.; Gendelman, H.E. Int. Rev. Neurobiol., 2007, 82, 297-325.
[http://dx.doi.org/10.1016/S0074-7742(07)82016-2] [PMID: 17678968]
[8]
De Lazzari, F.; Sandrelli, F.; Whitworth, A.J.; Bisaglia, M. Antioxidants, 2020, 9, 52.
[http://dx.doi.org/10.3390/antiox9010052]
[9]
Wang, L.; Cai, X.; Shi, M.; Xue, L.; Kuang, S.; Xu, R.; Qi, W.; Li, Y.; Ma, X.; Zhang, R.; Hong, F.; Ye, H.; Chen, L. Eur. J. Med. Chem., 2020, 199112385.
[http://dx.doi.org/10.1016/j.ejmech.2020.112385] [PMID: 32402936]
[10]
Sarubbo, F.; Moranta, D.; Asensio, V.J.; Miralles, A.; Esteban, S. Curr. Med. Chem., 2017, 24(38), 4245-4266.
[http://dx.doi.org/10.2174/0929867324666170724102743] [PMID: 28738770]
[11]
Nakajima, A.; Ohizumi, Y. Int. J. Mol. Sci., 2019, 20, 3380.
[http://dx.doi.org/10.3390/ijms20143380]
[12]
Ballesteros, J.A.; Weinstein, H. Methods Neurosci., 1995, 25, 366-428.
[http://dx.doi.org/10.1016/S1043-9471(05)80049-7]
[13]
Malo, M.; Brive, L.; Luthman, K.; Svensson, P. ChemMedChem, 2010, 5(2), 232-246.
[http://dx.doi.org/10.1002/cmdc.200900398] [PMID: 20077461]
[14]
Cowart, M.D.; Latshaw, S.P.; Nelson, S.L.; Stewart, A.O. U.S. patent, 20060172995. 2006.
[15]
Ksouda, G.; Sellimi, S.; Merlier, F.; Falcimaigne-Cordin, A.; Thomasset, B.; Nasri, M.; Hajji, M. Food Chem., 2019, 288, 47-56.
[http://dx.doi.org/10.1016/j.foodchem.2019.02.103] [PMID: 30902314]
[16]
Timotius, K.; Simamora, A.; Santoso, A.; Santoso, A. Pharmacogn. J., 2018, 10, 1114-1118.
[http://dx.doi.org/10.5530/pj.2018.6.189]
[17]
Košinová, P.; Meo, F.D.; Anouar, E.H.; Duroux, J-L.; Trouillas, P.H. Int. J. Quantum Chem., 2011, 111, 1131-1142.
[http://dx.doi.org/10.1002/qua.22555]
[18]
Han, R-M.; Zhang, J-P.; Skibsted, L.H. Molecules, 2012, 17(2), 2140-2160.
[http://dx.doi.org/10.3390/molecules17022140] [PMID: 22354191]
[19]
Weber, K.C.; Honório, K.M.; Bruni, A.T.; Andricopulo, A.D.; da Silva, A.B.F. Struct. Chem., 2006, 17, 307-313.
[http://dx.doi.org/10.1007/s11224-006-9048-7]
[20]
Scotti, L.; Scotti, M.T.; Pasqualoto, K.F.M. Rev. Bras. Farmacogn., 2009, 19, 908-913.
[21]
Johnson, E.R.; Keinan, S.; Mori-Sánchez, P.; Contreras-García, J.; Cohen, A.J.; Yang, W. J. Am. Chem. Soc., 2010, 132(18), 6498-6506.
[http://dx.doi.org/10.1021/ja100936w] [PMID: 20394428]
[22]
Yin, J.; Chen, K-Y.M.; Clark, M.J.; Hijazi, M.; Kumari, P.; Bai, X.; Sunahara, R.K.; Barth, P.; Rosenbaum, D.M. Nature, 2020, 1-5.
[23]
Jörg, M.; Kaczor, A.A.; Mak, F.S.; Lee, K.C.K.; Poso, A.; Miller, N.D.; Scammells, P.J.; Capuano, B. MedChemComm, 2014, 5, 891-898.
[http://dx.doi.org/10.1039/C4MD00066H]
[24]
Abraham, R.J.; Mobli, M. Magn. Reson. Chem., 2007, 45(10), 865-877.
[http://dx.doi.org/10.1002/mrc.2060] [PMID: 17729232]
[25]
Selent, J.; Marti-Solano, M.; Rodríguez, J.; Atanes, P.; Brea, J.; Castro, M.; Sanz, F.; Loza, M.I.; Pastor, M. Eur. J. Med. Chem., 2014, 77, 91-95.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.058] [PMID: 24631727]
[26]
Brea, J.; Castro, M.; Loza, M.I.; Masaguer, C.F.; Raviña, E.; Dezi, C.; Pastor, M.; Sanz, F.; Cabrero-Castel, A.; Galán-Rodríguez, B.; Fernández-Espejo, E.; Maldonado, R.; Robledo, P. Neuropharmacology, 2006, 51(2), 251-262.
[http://dx.doi.org/10.1016/j.neuropharm.2006.03.021] [PMID: 16697427]
[27]
Kaczor, A.A.; Silva, A.G.; Loza, M.I.; Kolb, P.; Castro, M.; Poso, A. ChemMedChem, 2016, 11(7), 718-729.
[http://dx.doi.org/10.1002/cmdc.201500599] [PMID: 26990027]
[28]
Kaczor, A.A.; Targowska-Duda, K.M.; Budzyńska, B.; Biała, G.; Silva, A.G.; Castro, M. Neurochem. Int., 2016, 96, 84-99.
[http://dx.doi.org/10.1016/j.neuint.2016.03.003] [PMID: 26964765]
[29]
Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision E.01, 2009.
[30]
MOE Molecular Operating Environment, 2009.
[31]
Kaczor, A.A.; Pitucha, M.; Karczmarzyk, Z.; Wysocki, W.; Rzymowska, J.; Matosiuk, D. Med. Chem., 2013, 9(3), 313-328.
[http://dx.doi.org/10.2174/1573406411309030002] [PMID: 22741788]
[32]
Contreras-García, J.; Johnson, E.R.; Keinan, S.; Chaudret, R.; Piquemal, J-P.; Beratan, D.N.; Yang, W. J. Chem. Theory Comput., 2011, 7(3), 625-632.
[http://dx.doi.org/10.1021/ct100641a] [PMID: 21516178]
[33]
Humphrey, W.; Dalke, A.; Schulten, K. J. Mol. Graph., 1996, 14(1), 33-38, 27-28.
[http://dx.doi.org/10.1016/0263-7855(96)00018-5] [PMID: 8744570]
[34]
Pitucha, M.; Sobotka-Polska, K.; Keller, R.; Pachuta-Stec, A.; Mendyk, E.; Kaczor, A.A. J. Mol. Struct., 2016, 1104, 24-32.
[http://dx.doi.org/10.1016/j.molstruc.2015.09.025]
[35]
www.wavefun.com
[36]
Bartyzel, A.; Kaczor, A.A. Polyhedron, 2018, 139, 271-281.
[http://dx.doi.org/10.1016/j.poly.2017.11.003]
[37]
Miertuš, S.; Scrocco, E. Tomasi. J. Chem. Phys., 1981, 55, 117-129.
[http://dx.doi.org/10.1016/0301-0104(81)85090-2]
[38]
Keith, T.A.; Bader, R.F.W. Chem. Phys. Lett., 1992, 194, 1-8.
[http://dx.doi.org/10.1016/0009-2614(92)85733-Q]
[39]
Keith, T.A.; Bader, R.F.W. Chem. Phys. Lett., 1993, 210, 223-231.
[http://dx.doi.org/10.1016/0009-2614(93)89127-4]
[40]
Cheeseman, J.R.; Trucks, G.W.; Keith, T.A.; Frisch, M.J. J. Chem. Phys., 1996, 104, 5497-5509.
[http://dx.doi.org/10.1063/1.471789]
[41]
http://cccbdb.nist.gov/vsf.asp
[42]
Jamróz, M.H. Vibrational Energy Distribution Analysis VEDA 4, Warsaw; , 2004.
[43]
Jamróz, M.H. Spectrochim. Acta A, 2013, 114, 220-230.
[http://dx.doi.org/10.1016/j.saa.2013.05.096]
[44]
Bartyzel, A.; Kaczor, A.A. J. Coord. Chem., 2015, 68, 3701-3717.
[http://dx.doi.org/10.1080/00958972.2015.1073268]
[45]
GaussView. Version 6.1, Roy Dennington, T/A; Keith, and J.M. Millam, Semichem Inc.: Shawnee Mission, KS, 2016.
[46]
http://www.chemcraftprog.com
[47]
http://www.arguslab.com
[48]
https://3dsbiovia.com/
[49]
Patel, J.Z.; Parkkari, T.; Laitinen, T.; Kaczor, A.A.; Saario, S.M.; Savinainen, J.R.; Navia-Paldanius, D.; Cipriano, M.; Leppänen, J.; Koshevoy, I.O.; Poso, A.; Fowler, C.J.; Laitinen, J.T.; Nevalainen, T. J. Med. Chem., 2013, 56(21), 8484-8496.
[http://dx.doi.org/10.1021/jm400923s] [PMID: 24083878]
[50]
Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. J. Med. Chem., 2006, 49(21), 6177-6196.
[http://dx.doi.org/10.1021/jm051256o] [PMID: 17034125]
[51]
Kondej, M.; Wróbel, T.M.; Silva, A.G.; Stępnicki, P.; Koszła, O.; Kędzierska, E.; Bartyzel, A.; Biała, G.; Matosiuk, D.; Loza, M.I.; Castro, M.; Kaczor, A.A. Eur. J. Med. Chem., 2019, 180, 673-689.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.050] [PMID: 31357129]
[52]
Kaczor, A.A.; Targowska-Duda, K.M.; Silva, A.G.; Kondej, M.; Biała, G.; Castro, M. Biomolecules, 2020, 10, 349.
[http://dx.doi.org/10.3390/biom10020349]
[53]
Release, S. 2019-4: Maestro; Schrödinger, LLC: New York, NY, 2019.
[54]
The PyMOL Molecular Graphics System. Version 2.0 Schrödinger, LLC,