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

Zeitschrift für Naturforschung B

A Journal of Chemical Sciences


IMPACT FACTOR 2017: 0.757

CiteScore 2017: 0.68

SCImago Journal Rank (SJR) 2017: 0.277
Source Normalized Impact per Paper (SNIP) 2017: 0.394

Online
ISSN
1865-7117
See all formats and pricing
More options …
Volume 71, Issue 4

Issues

Synthesis of structural analogues of GGT1-DU40, a potent GGTase-1 inhibitor

Muhammad Mansha
  • Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia
  • Centre of Research Excellence in Nanotechnology, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nisar Ullah
  • Corresponding author
  • Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Khalid Alhooshani
  • Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-03-18 | DOI: https://doi.org/10.1515/znb-2016-0019

Abstract

A series of new substituted pyrazoles 212 have been synthesized. The synthesized compounds are structural analogues of GGT1-DU40 1, a highly potent and selective inhibitor of protein geranylgeranyltransferase I (GGTase-I) both in vitro and in vivo. The implications of GGTase-I in oncogenesis have highlighted its potential as a cancer therapeutic target. Accordingly, the development of GGTase-I inhibitors has been a subject of much interest. The synthesis of 212 stemmed from the acetylation or acylation of N-function of amino acids to produce suitably modified amino acids. Meanwhile, the substituted pyrazole subunit originated from the reaction of ethyl nicotinate with γ-butyrolactone followed by condensation of the resultant β-keto lactone with (3,4-dichlorophenyl)hydrazine. The operations of O-alkylation and thioetherification on the resultant intermediate eventually produced the substituted pyrazole fragment. The amidation of the latter with amino acid derivatives finally rendered 212 in good to excellent yields.

Keywords: geranylgeranyltransferase I; GGT1-DU40; oncogenesis; protein prenylation; pyrazole-based inhibitors

References

  • [1]

    J. A. Glomset, M. H. Gelb, C. C. Farnsworth, Trends Biochem. Sci. 1990, 15, 139.CrossrefGoogle Scholar

  • [2]

    F. L. Zhang, P. J. Casey, Annu. Rev. Biochem. 1996, 65, 241.CrossrefGoogle Scholar

  • [3]

    P. J. Casey, M. C. Seabra, J. Biol. Chem. 1996, 271, 5289.CrossrefGoogle Scholar

  • [4]

    M. H. Gelb, L. Brunsveld, C. A. Hrycyna, S. Michaelis, F. Tamanoi, W. C. Van Voorhis, H. Waldmann, Nat. Chem. Biol. 2006, 2, 518.Google Scholar

  • [5]

    S. Maurer-Stroh, M. Koranda, W. Benetka, G. Schneider, F. L. Sirota, F. Eisenhaber, PLoS Comput. Biol. 2007, 3, e66.CrossrefGoogle Scholar

  • [6]

    M. N. Ashby, Curr. Opin. Lipidol. 1998, 9, 99.CrossrefGoogle Scholar

  • [7]

    A. M. Winter-Vann, P. J. Casey, Nat. Rev. Cancer 2005, 5, 405.CrossrefGoogle Scholar

  • [8]

    N. Berndt, A. D. Hamilton, S. M. Sebti, Nat. Rev. Cancer 2011, 11, 775.CrossrefGoogle Scholar

  • [9]

    R. J. Doll, P. Kirschmeier, W. R. Bishop, Curr. Opin. Drug Discov. Devel. 2004, 7, 478.Google Scholar

  • [10]

    C. A. Omer, Z. Chen, R. E. Diehl, M. W. Conner, H. Y. Chen, M. E. Trumbauer, S. Gopal-Truter, G. Seeburger, H. Bhimnathwala, M. T. Abrams, J. P. Davide, M. S. Ellis, J. B. Gibbs, I. Greenberg, K. S. Koblan, A. M. Kral, D. Liu, R. B. Lobell, P. J. Miller, S. D. Mosser, T. J. O’Neill, E. Rands, M. D. Schaber, E. T. Senderak, A. Oliff, N. E. Kohl, Cancer Res. 2000, 60, 2680.Google Scholar

  • [11]

    A. D. Basso, P. Kirschmeier, W. R. Bishop, J. Lipid Res. 2006, 47, 15.CrossrefGoogle Scholar

  • [12]

    D. B. Whyte, P. Kirschmeier, T. N. Hockenberry, I. Nunez-Oliva, L. James, J. J. Catino, W. R. Bishop, J. K. Pai, J. Biol. Chem. 1997, 272, 14459.CrossrefGoogle Scholar

  • [13]

    J. Sun, Y. Qian, A. D. Hamilton, S. M. Sebti, Oncogene 1998, 16, 1467.CrossrefGoogle Scholar

  • [14]

    J. Sun, M. A. Blaskovich, D. Knowles, Y. Qian, J. Ohkanda, R. D. Bailey, A. D. Hamilton, S. M. Sebti, Cancer Res. 1999, 59, 4919.Google Scholar

  • [15]

    S. M. Sebti, A. D. Hamilton, Oncogene 2000, 19, 6584.CrossrefGoogle Scholar

  • [16]

    K. M. Sane, M. Mynderse, D. T. LaLonde, I. S. Dean, J. W. Wojtkowiak, F. Fouad, R. F. Borch, J. J. Reiners, Jr., R. A. Gibbs, R. R. Mattingly, J. Pharmacol. Exp. Ther. 2010, 333, 23.CrossrefGoogle Scholar

  • [17]

    J. Lu, K. Yoshimura, K. Goto, C. Lee, K. Hamura, O. Kwon, F. Tamanoi, PLoS One 2015, 10, e0137595.Google Scholar

  • [18]

    A. K. Sjogren, K. M. Andersson, M. Liu, B. A. Cutts, C. Karlsson, A. M. Wahlstrom, M. Dalin, C. Weinbaum, P. J. Casey, A. Tarkowski, B. Swolin, S. G. Young, M. O. Bergo, J. Clin. Invest. 2007, 117, 1294.CrossrefGoogle Scholar

  • [19]

    N. Ullah. Z. Naturforsch. 2012, 67b, 75.Google Scholar

  • [20]

    N. Ullah, A. A. Q. Al-Shaheri, Z. Naturforsch. 2012, 67b, 253.CrossrefGoogle Scholar

  • [21]

    N. Ullah, J. Enzyme Inhib. Med. Chem. 2014, 29, 281.CrossrefGoogle Scholar

  • [22]

    N. Ullah, Med. Chem. 2014, 10, 484.Google Scholar

  • [23]

    Y. K. Peterson, P. Kelly, C. A. Weinbaum, P. J. Casey, J. Biol. Chem. 2006, 281, 12445.Google Scholar

  • [24]

    G. Naturale, M. Lamblin, C. Commandeur, F.-X. Felpin, J. Dessolin, Eur. J. Org. Chem. 2012, 29, 5774.CrossrefGoogle Scholar

  • [25]

    T. Polonski, Tetrahedron 1985, 41, 603.CrossrefGoogle Scholar

  • [26]

    K. Guzow, R. Ganzynkowicz, A. Rzeska, J. Mrozek, M. Szabelski, J. Karolczak, A. Liwo, W. Wiczk, J. Phys. Chem. B. 2004, 108, 3879.CrossrefGoogle Scholar

  • [27]

    N.-N. Liu, S.-M. Zhao, J.-F. Zhao, G.-Z. Zeng, N.-H. Tan, J.-P. Liu, Tetrahedron 2014, 70, 6630.CrossrefGoogle Scholar

  • [28]

    C. L. Millington, A. J. Watson, A. S. Marriott, G. P. Margison, A. C. Povey, D. M. Williams, Nucleos. Nucleot. Nucl. 2012, 31, 328.CrossrefGoogle Scholar

  • [29]

    M. G. Campbell, Z. Guo, F. F. Li, K. S. Rehder, J.-P. Strachan, C. P. Viscardi, WO2004016592, 2004.Google Scholar

  • [30]

    H. Fiji, O. Kwon, F. Tamanoi, M. Watanabe, WO2007111948, 2007.Google Scholar

  • [31]

    O. Kwon, F. Tamanoi, H. Fiji, M. Watanabe, WO2010014054, 2010.Google Scholar

About the article

Corresponding author: Nisar Ullah, Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia, Fax: +966 3 860 4277, E-mail:


Received: 2016-01-18

Accepted: 2016-02-09

Published Online: 2016-03-18

Published in Print: 2016-04-01


Citation Information: Zeitschrift für Naturforschung B, Volume 71, Issue 4, Pages 333–344, ISSN (Online) 1865-7117, ISSN (Print) 0932-0776, DOI: https://doi.org/10.1515/znb-2016-0019.

Export Citation

©2016 by De Gruyter.Get Permission

Comments (0)

Please log in or register to comment.
Log in