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Zeitschrift für Naturforschung B

A Journal of Chemical Sciences

IMPACT FACTOR 2017: 0.757

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Volume 71, Issue 4


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:
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/ Nisar Ullah
  • Corresponding author
  • Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia
  • Email
  • Other articles by this author:
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/ Khalid Alhooshani
  • Chemistry Department, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia
  • Other articles by this author:
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Published Online: 2016-03-18 | DOI: https://doi.org/10.1515/znb-2016-0019


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


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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.

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