Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Pure and Applied Chemistry

The Scientific Journal of IUPAC

Ed. by Burrows, Hugh / Weir, Ron / Stohner, Jürgen

12 Issues per year


IMPACT FACTOR 2016: 2.626
5-year IMPACT FACTOR: 3.210

CiteScore 2016: 2.45

SCImago Journal Rank (SJR) 2016: 0.972
Source Normalized Impact per Paper (SNIP) 2016: 1.049

Online
ISSN
1365-3075
See all formats and pricing
More options …
Volume 88, Issue 4 (Apr 2016)

Issues

Synthesis of glucopyranos-6′-yl purine and pyrimidine isonucleosides as potential cholinesterase inhibitors. Access to pyrimidine-linked pseudodisaccharides through Mitsunobu reaction

Daniela BatistaORCID iD: http://orcid.org/0000-0002-5084-2113 / Stefan SchwarzORCID iD: http://orcid.org/0000-0003-0566-2436 / Anne LoescheORCID iD: http://orcid.org/0000-0002-7147-6677 / René CsukORCID iD: http://orcid.org/0000-0001-7911-290X / Paulo J. CostaORCID iD: http://orcid.org/0000-0002-0492-6666 / M. Conceição OliveiraORCID iD: http://orcid.org/0000-0002-3068-4920 / Nuno M. XavierORCID iD: http://orcid.org/0000-0001-8739-8768
Published Online: 2016-04-19 | DOI: https://doi.org/10.1515/pac-2016-0102

Abstract

The synthesis of new isonucleosides comprising purine and pyrimidine-derived systems linked to methyl glucopyranosidyl units at C-6 and evaluation of their cholinesterase inhibitory profiles is reported. Their access was based on the Mitsunobu coupling of partially acetylated and benzylated methyl glucopyranosides with purine and pyrimidine derivatives. While the reactions with purines and theobromine proceeded with complete regioselectivity, affording exclusively N9- or N1-linked 6′-isonucleosides, respectively, the use of pyrimidine nucleobases led to N1 and/or N3-glucopyranosid-6′-yl pyrimidines and/or to N1,N3/2-O,4-O-pyrimidine-linked pseudodisaccharides through bis-coupling, depending on the substitution pattern of the sugar precursor and on the nature of the nucleobase. From this series of compounds, four were shown to be effective and selective inhibitors of acetylcholinesterase with inhibition constants in the micromolar concentration range. A tri-O-acetylated N1-glucopyranosid-6′-yl theobromine and a benzylated N1,N3-bis-glucopyranosid-6-yl thymine were the most active molecules with Ki values of 4 μM. A tri-O-benzylated glucopyranosid-6′-yl uracil displayed good and selective inhibition of butyrylcholinesterase (Ki=8.4±1.0 μM), similar to that exhibited by the standard galantamine. Molecular docking simulations, performed with the two most effective acetylcholinesterase inhibitors, showed interactions with key amino acid residues located at the enzyme’s active site gorge, which explain the competitive component of their inhibitory activities.

Keywords: bioactive molecules; cholinesterases; enzyme inhibitors; ESOC-19; isonucleosides; Mitsunobu coupling; pseudodisaccharides

Article note:

A collection of invited papers based on presentations at the 19th European Symposium on Organic Chemistry (ESOC-19), Lisbon, Portugal, 12–16 July 2015.

References

  • [1]

    L. P. Jordheim, D. Durantel, F. Zoulim, C. Dumontet. Nat. Rev. Drug. Discov. 12, 447 (2013).Google Scholar

  • [2]

    S. Knapp. Chem. Rev. 95, 185 (1995).Google Scholar

  • [3]

    K.-i. Kimura, T. D. H. Bugg. Nat. Prod. Rep. 20, 252 (2003).Google Scholar

  • [4]

    S. Rachakonda, L. Cartee. Curr. Med. Chem. 11, 775 (2004).Google Scholar

  • [5]

    M. Winn, R. J. M. Goss, K.-i. Kimura, T. D. H. Bugg. Nat. Prod. Rep. 27, 279 (2010).Google Scholar

  • [6]

    L. A. Vitali, D. Petrelli, C. Lambertucci, M. Prenna, R. Volpini, G. Cristalli. J. Med. Microbiol. 61, 525 (2012).Google Scholar

  • [7]

    C. Meier, C. Ducho, U. Görbig, R. Esnouf, J. Balzarini. J. Med. Chem. 47, 2839 (2004).Google Scholar

  • [8]

    S. Schwarz, R. Csuk, A. P. Rauter. Org. Biomol. Chem. 12, 2446 (2014).Google Scholar

  • [9]

    N. M. Xavier, S. Schwarz, P. D. Vaz, R. Csuk, A. P. Rauter. Eur. J. Org. Chem. 2014, 2770 (2014).Google Scholar

  • [10]

    P. Anand, B. Singh. Arch. Pharmacal. Res. 36, 375 (2013).Google Scholar

  • [11]

    W. J. Deardorff, E. Feen, G. T. Grossberg. Drugs Aging 32, 537 (2015).Google Scholar

  • [12]

    H. W. Yu, L. R. Zhang, J. C. Zhuo, L. T. Ma, L. H. Zhang. Bioorg. Med. Chem. 4, 609 (1996).Google Scholar

  • [13]

    H.-W. Yu, H.-Y. Zhang, Z.-J. Yang, J.-M. Min, L.-T. Ma, L.-H. Zhang. Pure Appl. Chem. 70, 435 (1998).Google Scholar

  • [14]

    D. M. Huryn, B. C. Sluboski, S. Y. Tam, M. Weigele, I. Sim, B. D. Anderson, H. Mitsuya, S. Broder. J. Med. Chem. 35, 2347 (1992).Google Scholar

  • [15]

    J. A. Tino, J. M. Clark, A. K. Field, G. A. Jacobs, K. A. Lis, T. L. Michalik, B. McGeever-Rubin, W. A. Slusarchyk, S. H. Spergel. J. Med. Chem. 36, 1221 (1993).Google Scholar

  • [16]

    K. F. Solke, J.-L. Huang, J. W. Russell, V. J. Whiterock, J. E. Sundeen, L. W. Stratton, J. M. Clark. Antiviral Res. 23, 219 (1994).Google Scholar

  • [17]

    V. Nair, M. H. St. Clair, J. E. Reardon, H. C. Krasny, R. J. Hazen, M. T. Paff, L. R. Boone, M. Tisdale, I. Najera, R. E. Dornsife, D. R. Averett, K. Borroto-Esoda, J. L. Yale, T. P. Zimmerman, J. L. Rideout. Antimicrob. Agents Chemother. 39, 1993 (1995).Google Scholar

  • [18]

    V. Nair. in Recent Advances in Nucleosides: Chemistry and Chemotherapy, C. K. Chu, (Ed.), pp. 149–166, Elsevier, Oxford (2002).Google Scholar

  • [19]

    V. Nair, D. G. Piotrowska, M. Okello, J. Vadakkan. Nucleos. Nucleot. Nucl. 26, 687 (2007).Google Scholar

  • [20]

    S. Aragonès, F. Bravo, Y. Díaz, M. I. Matheu, S. Castillón. Tetrahedron Lett. 44, 3771 (2003).Google Scholar

  • [21]

    J. Zhang, Y. Chen, Y. Huang, H.-W. Jin, R.-P. Qiao, L. Xing, L.-R. Zhang, Z.-J. Yang, L.-H. Zhang. Org. Biomol. Chem. 10, 7566 (2012).Google Scholar

  • [22]

    Y. Yoshimura, K. Asami, H. Matsui, H. Tanaka, H. Takahata. Org. Lett. 8, 6015 (2006).Google Scholar

  • [23]

    A. Chattopadhyay, A. Salaskar. J. Chem. Soc., Perkin Trans. 16, 785 (2002).Google Scholar

  • [24]

    L. S. Jeong, S. J. Yoo, H. R. Moon, M. W. Chun, C.-K. Lee. Nucleos. Nucleot. 18, 655 (1999).Google Scholar

  • [25]

    N. M. Xavier, S. D. Lucas, R. Jorda, S. Schwarz, A. Loesche, R. Csuk, M. C. Oliveira. Synlett. 26, 2663 (2015).Google Scholar

  • [26]

    S. Bera, V. Nair. Tetrahedron Lett. 42, 5813 (2001).Google Scholar

  • [27]

    P. J. Bolon, T. B. Sells, Z. M. Nuesca, D. F. Purdy, V. Nair. Tetrahedron 50, 7747 (1994).Google Scholar

  • [28]

    C. Besset, S. Chambert, Y. Queneau, S. Kerverdo, H. Rolland, J. Guilbot. Carbohydr. Res. 343, 929 (2008).Google Scholar

  • [29]

    C. Besset, S. Chambert, B. Fenet, Y. Queneau. Tetrahedron Lett. 50, 7043 (2009).Google Scholar

  • [30]

    M. R. L, S. K. Yousuf, D. Mukherjee, S. C. Taneja. Org. Biomol. Chem. 10, 9090 (2012).Google Scholar

  • [31]

    A. R. Dar, M. A. Aga, B. Kumar, S. K. Yousuf, S. C.Taneja. Org. Biomol. Chem. 11, 6195 (2013).Google Scholar

  • [32]

    M. Yang, S. W. Schneller, B. B. Korba. J. Med. Chem. 48, 5043 (2005).Google Scholar

  • [33]

    Y. Kitade, T. Ando, T. Yamaguchi, A. Hori, M. Nakanishi, Y. Ueno. Bioorg. Med. Chem. 14, 5578 (2006).Google Scholar

  • [34]

    H. Ashihara, T. Suzuki. Front. Biosci. 9, 1864 (2004).Google Scholar

  • [35]

    H. Ashihara, T. Yokota, A. Crozier. Adv. Bot. Res. 68, 111 (2013).Google Scholar

  • [36]

    J. A. Elvidge, G. T. Rogers, T. L. V. Ulbricht. J. Heterocyclic Chem. 8, 1039 (1971).Google Scholar

  • [37]

    B.-K. Chun, P. Wang, A. Hassan, J. Du, P. M. Tharnish, L. J. Stuyver, M. J. Otto, R. F. Schinazi, K. A. Watanabe. Tetrahedron Lett. 46, 2825 (2005).Google Scholar

  • [38]

    B.-K. Chun, P. Wang, A. Hassan, J. Du, P. M. Tharnish, E. Murakami, L. Stuyver, M. J. Otto. Nucleos. Nucleot. Nucl. 26, 83 (2007).Google Scholar

  • [39]

    M. Pohanka, P. Dobes. Int. J. Mol. Sci. 14, 9873 (2013).Google Scholar

  • [40]

    T. Mohamed, W. Osman, G. Tin, P. P. N. Rao. Bioorg. Med. Chem. Lett. 23, 4336 (2013).Google Scholar

  • [41]

    D. Beer, G. Bhalay, A. Dunstan, A. Glen, S. Haberthuer, H. Moser. Bioorg. Med. Chem. Lett. 12, 1973 (2002).Google Scholar

  • [42]

    A. Dondoni, A. Massi, S. Sabbatini, V. Bertolasi. J. Org.Chem. 67, 6979 (2002).Google Scholar

  • [43]

    A. Marra, A. Vecchi, C. Chiappe, B. Melai, A. Dondoni. J. Org. Chem. 73, 2458 (2008).Google Scholar

  • [44]

    P.-Z. Zhang, X.-L. Li, H. Chen, Y.-N. Li, R. Wang. Tetrahedron Lett. 48, 7813 (2007).Google Scholar

  • [45]

    P. Zhang, C. Wei, E. Wang, W. Wanga, M. Liu, Q. Yin, H. Chen, K. Wang, X. Li, J. Zhang. Carbohydr. Res. 351, 7 (2012).Google Scholar

  • [46]

    A. Kayet, T. Pathak. J. Org. Chem. 78, 9865 (2013).Google Scholar

  • [47]

    M.-H. Huang, J. Duchek, A. Vasella. Molecules 18, 3906 (2013).Google Scholar

  • [48]

    H. Sugimura, K. Stansfield. Synlett. 1998, 985 (1998).Google Scholar

  • [49]

    K. Stansfield, H. Kanamori, H. Sugimura. New J. Chem. 23, 9 (1999).Google Scholar

  • [50]

    T. G. George, P. Szolcsányi, S. G. Koenig, D. E. Paterson, Y. Isshiki, A. Vasella. Helv. Chim. Acta 87, 1287 (2004).Google Scholar

  • [51]

    M. Breugst, F. C. Bautista, H. Mayr. Chem. Eur. J. 18, 127 (2012).Google Scholar

  • [52]

    G. Mushtaq, N. H. Greig, J. A. Khan, M. A. Kamal. CNS Neurol. Disord. Drug Targets 13, 1432 (2014).Google Scholar

  • [53]

    O. Trott, A. J. Olson. J. Comput. Chem. 31, 455 (2010).Google Scholar

  • [54]

    G. Kryger, M. Harel, K. Giles, L. Toker, B. Velan, A. Lazar, C. Kronman, D. Barak, N. Ariel, A. Shafferman, I. Silman, J. L. Sussman. Acta Crystallogr. D Biol. Crystallogr. 56, 1385 (2000).Google Scholar

  • [55]

    PyMOL Molecular Graphics System, Version 1.2r2, DeLano Scientific LLC, 2009.

  • [56]

    H. Lineweaver, D. Burk. J. Am. Chem. Soc. 56, 658 (1934).Google Scholar

  • [57]

    M. Dixon. Biochem. J. 55, 170 (1953).Google Scholar

  • [58]

    A. Cornish-Bowden. Biochem. J. 137, 143 (1974).Google Scholar

  • [59]

    H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, P. E. Bourne. Nucleic Acids Res. 28, 235 (2000).Google Scholar

  • [60]

    Gaussian 09, Revision E.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, and D. J. Fox, Gaussian, Inc., Wallingford CT, 2009.

  • [61]

    C. Adamo, V. Barone. J. Chem. Phys. 110, 6158 (1999).Google Scholar

  • [62]

    C. I. Bayly, P. Cieplak, W. Cornell, P. A. Kollman. J. Phys. Chem. 97, 10269 (1993).Google Scholar

  • [63]

    G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew, D. S. Goodsell, A. J. Olson. J. Comput. Chem. 30, 2785 (2009).Google Scholar

  • [64]

    M. F. Sanner. J. Mol. Graph. Model 17, 57 (1999).Google Scholar

About the article

Published Online: 2016-04-19

Published in Print: 2016-04-01


Citation Information: Pure and Applied Chemistry, ISSN (Online) 1365-3075, ISSN (Print) 0033-4545, DOI: https://doi.org/10.1515/pac-2016-0102.

Export Citation

©2016 IUPAC & De Gruyter. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. For more information, please visit: http://creativecommons.org/licenses/by-nc-nd/4.0/. Copyright Clearance Center

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Nuno M. Xavier, Rita Gonçalves-Pereira, Radek Jorda, Eva Řezníčková, Vladimír Kryštof, and M. Conceição Oliveira
Pure and Applied Chemistry, 2017, Volume 89, Number 9

Comments (0)

Please log in or register to comment.
Log in