European Journal of Chemistry

Crystal structure, in silico molecular docking, DFT analysis and ADMET studies of N-(2-methoxy-benzyl)-acetamide

Crossmark


Main Article Content

Suganya Murugan
Prasanth Gunasekaran
Jayasudha Nehru
Anaglit Catherine Paul
Necmi Dege
Emine Berrin Cinar
Savaridasson Jose Kavitha
Kasthuri Balasubramani
Kaliyaperumal Thanigaimani
Venkatachalam Rajakannan
Madhukar Hemamalini

Abstract

In this work, N-(2-methoxy-benzyl)-acetamide (2MBA) was synthesized from an amide derivative and it was characterized by FT-IR and NMR spectroscopy techniques. The crystal structure of 2MBA was also validated via single-crystal X-ray diffraction analysis. Crystal data for C10H13NO2 for 2MBA: Monoclinic, space group P21/n (no. 14), a = 9.1264(6) Å, b = 9.3375(7) Å, c = 11.9385(8) Å, β = 95.745(5)°, = 1012.26(12) Å3, Z = 4, μ(MoKα) = 0.082 mm-1, Dcalc = 1.176 g/cm3, 5632 reflections measured (5.368° ≤ 2Θ ≤ 51.992°), 1990 unique (Rint = 0.0377, Rsigma = 0.0314) which were used in all calculations. The final R1 was 0.0583 (I > 2σ(I)) and wR2 was 0.1444 (all data).  The intermolecular interactions in 2MBA were theoretically examined by Hirshfeld surface analysis and 2D fingerprint plots. Moreover, the HOMO and LUMO energy gaps of 2MBA was calculated by DFT calculation with the B3LYP/6-311G++(d,p) method. The electron-withdrawing and donating sites of the 2MBA were confirmed via molecular electrostatic potential surface analysis. The present study discusses the title compound not only highlighted the crystallographic data but also revealed good molecular interactions together with an anticancer drug target, which is a targeting PARP protein, which was an important drug target in the treatment of breast cancer.


icon graph This Abstract was viewed 659 times | icon graph Article PDF downloaded 349 times icon graph Article CIF FILE downloaded 0 times

How to Cite
(1)
Murugan, S.; Gunasekaran, P.; Nehru, J.; Paul, A. C.; Dege, N.; Cinar, E. B.; Kavitha, S. J.; Balasubramani, K.; Thanigaimani, K.; Rajakannan, V. Crystal Structure, in Silico Molecular Docking, DFT Analysis and ADMET Studies of N-(2-Methoxy-Benzyl)-Acetamide. Eur. J. Chem. 2022, 13, 440-450.

Article Details

Share
Crossref - Scopus - Google - European PMC
References

[1]. Humphrey, J. M.; Chamberlin, A. R. Chemical synthesis of natural product peptides: Coupling methods for the incorporation of noncoded amino acids into peptides. Chem. Rev. 1997, 97, 2243-2266.
https://doi.org/10.1021/cr950005s

[2]. Ghose, A. K.; Viswanadhan, V. N.; Wendoloski, J. J. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J. Comb. Chem. 1999, 1, 55-68.
https://doi.org/10.1021/cc9800071

[3]. Walsh, G. Pharmaceutical Biotechnology: Concepts and Applications; 1st ed.; John Wiley & Sons: Nashville, TN, 2013.

[4]. Khalid, H.; Aziz-ur-Rehman; Abbasi, M. A.; Malik, A.; Rasool, S.; Nafeesa, K.; Ahmad, I.; Afzal, S. Synthesis, spectral analysis and anti-bacterial study of N -substituted derivatives of 2-(5-(1-(phenylsulfonyl) piperidin-4-yl)-1,3,4-oxadiazol-2-ylthio)acetamide. J. Saudi Chem. Soc. 2016, 20, S615-S623.
https://doi.org/10.1016/j.jscs.2013.05.001

[5]. Autore, G.; Caruso, A.; Marzocco, S.; Nicolaus, B.; Palladino, C.; Pinto, A.; Popolo, A.; Sinicropi, M. S.; Tommonaro, G.; Saturnino, C. Acetamide derivatives with antioxidant activity and potential anti-inflammatory activity. Molecules 2010, 15, 2028-2038.
https://doi.org/10.3390/molecules15032028

[6]. Hazra, B.; Pore, V.; Dey, S.; Datta, S.; Darokar, M.; Saikia, D.; Khanuja, S. P. S.; Thakur, A. Bile acid amides derived from chiral amino alcohols: novel antimicrobials and antifungals. Bioorg. Med. Chem. Lett. 2004, 14, 773-777.
https://doi.org/10.1016/j.bmcl.2003.11.018

[7]. Sawant, R.; Kawade, D. Synthesis and biological evaluation of some novel 2-phenyl benzimidazole-1-acetamide derivatives as potential anthelmintic agents. Acta Pharm. 2011, 61, 353-361.
https://doi.org/10.2478/v10007-011-0029-z

[8]. Hu, J.; Yu, M.; Yu, P.; Xu, Y. Synthesis and antimicrobial activity of novel benzisothiazolin-3-one acetamide derivatives. Asian J. Chem. 2014, 26, 7680-7682.
https://doi.org/10.14233/ajchem.2014.17594

[9]. Shridhar Deshpande, N.; Mahendra, G. S.; Aggarwal, N. N.; Gatphoh, B. F. D.; Revanasiddappa, B. C. Insilico design, ADMET screening, MM-GBSA binding free energy of novel 1,3,4 oxadiazoles linked Schiff bases as PARP-1 inhibitors targeting breast cancer. Futur. J. Pharm. Sci. 2021, 7, 174.
https://doi.org/10.1186/s43094-021-00321-4

[10]. Daina, A.; Michielin, O.; Zoete, V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017, 7, 42717.
https://doi.org/10.1038/srep42717

[11]. Filimonov, D. A.; Lagunin, A. A.; Gloriozova, T. A.; Rudik, A. V.; Druzhilovskii, D. S.; Pogodin, P. V.; Poroikov, V. V. Prediction of the biological activity spectra of organic compounds using the pass online web resource. Chem. Heterocycl. Compd. (N. Y.) 2014, 50, 444-457.
https://doi.org/10.1007/s10593-014-1496-1

[12]. Morris, G. M.; Huey, R.; Lindstrom, W.; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 2009, 30, 2785-2791.
https://doi.org/10.1002/jcc.21256

[13]. Karlberg, T.; Markova, N.; Johansson, I.; Hammarström, M.; Schütz, P.; Weigelt, J.; Schüler, H. Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor. J. Med. Chem. 2010, 53, 5352-5355.
https://doi.org/10.1021/jm100249w

[14]. Ryan, K.; Bolaňos, B.; Smith, M.; Palde, P. B.; Cuenca, P. D.; VanArsdale, T. L.; Niessen, S.; Zhang, L.; Behenna, D.; Ornelas, M. A.; Tran, K. T.; Kaiser, S.; Lum, L.; Stewart, A.; Gajiwala, K. S. Dissecting the molecular determinants of clinical PARP1 inhibitor selectivity for tankyrase1. J. Biol. Chem. 2021, 296, 100251.
https://doi.org/10.1074/jbc.RA120.016573

[15]. Yang, X.; Sun, R.; Zhang, C.; Zheng, X.; Yuan, M.; Fu, H.; Li, R.; Chen, H. Iridium-catalyzed benzylamine C-H alkenylation enabled by pentafluorobenzoyl as the directing group. Org. Lett. 2019, 21, 1002-1006.
https://doi.org/10.1021/acs.orglett.8b04005

[16]. Mumtaz, A.; Mahmud, T.; Mr, E. Synthesis and characterization of new Schiff base transition metal complexes derived from drug together with biological potential study. J. Nucl. Med. Radiat. Ther. 2016, 07, 6.
https://doi.org/10.4172/2155-9619.1000310

[17]. Narasimharao, K.; Chemistry Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia Design, spectroscopic characterization, electrical conductivity and molecular modelling studies of biologically puissant Co(II) and Ni(II) complexes of N,N'-bis(furan-2-ylmethyl)benzene-1,2- dicarboxamide. Int. J. Electrochem. Sci. 2016, 7282-7307.
https://doi.org/10.20964/2016.08.43

[18]. Bruker (2015). APEX3. Bruker AXS Inc., Madison, Wisconsin, USA.

[19]. Bruker (2008). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.

[20]. Sheldrick, G. M. A short history of SHELX. Acta Crystallogr. A 2008, 64, 112-122.
https://doi.org/10.1107/S0108767307043930

[21]. Spek, A. L. Structure validation in chemical crystallography. Acta Crystallogr. D Biol. Crystallogr. 2009, 65, 148-155.
https://doi.org/10.1107/S090744490804362X

[22]. Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. OLEX2: a complete structure solution, refinement and analysis program. J. Appl. Crystallogr. 2009, 42, 339-341.
https://doi.org/10.1107/S0021889808042726

[23]. Farrugia, L. J. ORTEP-3 for Windows - a version of ORTEP-III with a Graphical User Interface (GUI). J. Appl. Crystallogr. 1997, 30, 565-565.
https://doi.org/10.1107/S0021889897003117

[24]. Spackman, P. R.; Turner, M. J.; McKinnon, J. J.; Wolff, S. K.; Grimwood, D. J.; Jayatilaka, D.; Spackman, M. A. CrystalExplorer: a program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals. J. Appl. Crystallogr. 2021, 54, 1006-1011.
https://doi.org/10.1107/S1600576721002910

[25]. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 09, rev. A.01, Gaussian, Inc., Wallingford CT, 2013.

[26]. Bhabha, G.; Ekiert, D. C.; Jennewein, M.; Zmasek, C. M.; Tuttle, L. M.; Kroon, G.; Dyson, H. J.; Godzik, A.; Wilson, I. A.; Wright, P. E. Divergent evolution of protein conformational dynamics in dihydrofolate reductase. Nat. Struct. Mol. Biol. 2013, 20, 1243-1249.
https://doi.org/10.1038/nsmb.2676

[27]. Blanco, B.; Prado, V.; Lence, E.; Otero, J. M.; Garcia-Doval, C.; van Raaij, M. J.; Llamas-Saiz, A. L.; Lamb, H.; Hawkins, A. R.; González-Bello, C. Mycobacterium tuberculosis shikimate kinase inhibitors: Design and simulation studies of the catalytic turnover. J. Am. Chem. Soc. 2013, 135, 12366-12376.
https://doi.org/10.1021/ja405853p

[28]. Ritchie, T. J.; Ertl, P.; Lewis, R. The graphical representation of ADME-related molecule properties for medicinal chemists. Drug Discov. Today 2011, 16, 65-72.
https://doi.org/10.1016/j.drudis.2010.11.002

[29]. Dunnett, C. W. New tables for multiple comparisons with a control. Biometrics 1964, 20, 482-491.
https://doi.org/10.2307/2528490

[30]. Tung, N.; Garber, J. E. PARP inhibition in breast cancer: progress made and future hopes. NPJ Breast Cancer 2022, 8, 47.
https://doi.org/10.1038/s41523-022-00411-3

[31]. Qiu, W.; Lam, R.; Voytyuk, O.; Romanov, V.; Gordon, R.; Gebremeskel, S.; Vodsedalek, J.; Thompson, C.; Beletskaya, I.; Battaile, K. P.; Pai, E. F.; Rottapel, R.; Chirgadze, N. Y. Insights into the binding of PARP inhibitors to the catalytic domain of human tankyrase-2. Acta Crystallogr. D Biol. Crystallogr. 2014, 70, 2740-2753.
https://doi.org/10.1107/S1399004714017660

[32]. DeLano, W. L. The PyMOL Molecular Graphics System DeLano Scientific: San Carlos, CA, 2002. https://www.pymol.org (accessed August 10, 2022).

[33]. Wallace, A. C.; Laskowski, R. A.; Thornton, J. M. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng. Des. Sel. 1995, 8, 127-134.
https://doi.org/10.1093/protein/8.2.127

[34]. Schöning-Stierand, K.; Diedrich, K.; Fährrolfes, R.; Flachsenberg, F.; Meyder, A.; Nittinger, E.; Steinegger, R.; Rarey, M. ProteinsPlus: interactive analysis of protein-ligand binding interfaces. Nucleic Acids Res. 2020, 48, W48-W53.
https://doi.org/10.1093/nar/gkaa235

[35]. Stierand, K.; Maass, P. C.; Rarey, M. Molecular complexes at a glance: automated generation of two-dimensional complex diagrams. Bioinformatics 2006, 22, 1710-1716.
https://doi.org/10.1093/bioinformatics/btl150

[36]. Kansiz, S.; Çakmak, S.; Dege, N.; Meral, G.; Kütük, H. Crystal Structure of 3-Acetoxy-2-methyl-N-(4-nitrophenyl)benzamide. X-ray Struct. Anal. Online 2018, 34, 17-18.
https://doi.org/10.2116/xraystruct.34.17

[37]. Mackenzie, C. F.; Spackman, P. R.; Jayatilaka, D.; Spackman, M. A. CrystalExplorer model energies and energy frameworks: extension to metal coordination compounds, organic salts, solvates and open-shell systems. IUCrJ 2017, 4, 575-587.
https://doi.org/10.1107/S205225251700848X

[38]. Abbaz, T.; Bendjeddou, A.; Villemin, D. Molecular structure, HOMO, LUMO, MEP, natural bond orbital analysis of benzo and anthra quinodimethane derivatives. Pharm. Biol. Evaluations 2018, 5, 27-39.
https://doi.org/10.26510/2394-0859.pbe.2018.04

[39]. Uzun, S.; Esen, Z.; Koç, E.; Usta, N. C.; Ceylan, M. Experimental and density functional theory (MEP, FMO, NLO, Fukui functions) and antibacterial activity studies on 2-amino-4-(4-nitrophenyl)-5,6-dihydrobenzo[h]quinoline-3-carbonitrile. J. Mol. Struct. 2019, 1178, 450-457.
https://doi.org/10.1016/j.molstruc.2018.10.001

[40]. Cortesi, L.; Rugo, H. S.; Jackisch, C. An overview of PARP inhibitors for the treatment of breast cancer. Target. Oncol. 2021, 16, 255-282.
https://doi.org/10.1007/s11523-021-00796-4

[41]. Griguolo, G.; Dieci, M. V.; Guarneri, V.; Conte, P. Olaparib for the treatment of breast cancer. Expert Rev. Anticancer Ther. 2018, 18, 519-530.
https://doi.org/10.1080/14737140.2018.1458613

[42]. Litton, J. K.; Rugo, H. S.; Ettl, J.; Hurvitz, S. A.; Gonçalves, A.; Lee, K.-H.; Fehrenbacher, L.; Yerushalmi, R.; Mina, L. A.; Martin, M.; Roché, H.; Im, Y.-H.; Quek, R. G. W.; Markova, D.; Tudor, I. C.; Hannah, A. L.; Eiermann, W.; Blum, J. L. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N. Engl. J. Med. 2018, 379, 753-763.
https://doi.org/10.1056/NEJMoa1802905

Supporting Agencies

The Science and Engineering Research Board Science, International Research Experience (SERB-IRE) (SIR/2022/000011) and Mother Teresa Women’s University, Tamil Nadu, India.
Most read articles by the same author(s)
TrendMD

Dimensions - Altmetric - scite_ - PlumX

Downloads and views

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...
License Terms

License Terms

by-nc

Copyright © 2024 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at https://www.eurjchem.com/index.php/eurjchem/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution, or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (https://www.eurjchem.com/index.php/eurjchem/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry).