The Open Medicinal Chemistry Journal

ISSN: 1874-1045 ― Volume 13, 2019

Discovery of Iminobenzimidazole Derivatives as Novel Cytotoxic Agents

Nora Chouha1, 3, Hassan Hammoud1, Simone Brogi4, Giuseppe Campiani4, Caroline Welsch5, 6, Caroline Robert5, 7, Stéphan Vagner8, Thierry Cresteil9, Embarek Bentouhami1, 10, Laurent Désaubry1, 2, *
1 Laboratory of Therapeutic Innovation (UMR 7200), Faculty of Pharmacy, University of Strasbourg–CNRS, 67401, Illkirch, France
2 Laboratory of Biomolecules (UMR7203), CNRS-Sorbonne University, 4 place Jussieu, 75005Paris, France
3 Laboratory of Synthesis of Molecules of Biological Interest, Université des Frères Mentouri Constantine 1, 25000 Constantine, Algeria
4 European Research Centre for Drug Discovery (Nat SynDrugs), Department of Biotechnology, Chemistry and Pharmacy (DBCF), University of Siena, Siena, Italy
5 INSERM U981, Gustave Roussy Cancer Campus, Villejuif, France
6 Université Paris-Sud, Université Paris-Saclay, Kremlin-Bicêtre, France
7 Department of Oncology, Gustave Roussy Cancer Campus, Villejuif, France
8 Institut Curie, PSL Research University, CNRS UMR3348,91405, Orsay, France
9 IPSIT, Faculty of Pharmacy, Université Paris-Sud, 92290 Chatenay-Malabry, France
10 Laboratory of Chemistry, Molecular Engineering and Nanostructures (LCIMN), University Ferhat Abbas- Sétif 1, Sétif, Algeria


In our quest to identify inhibitors of the eukaryotic translation initiation factor 4F (eIF4F), we serendipitously discovered a novel cytotoxic agent. Even though this compound did not inhibit translation, we explored the structural requirements for its cytotoxicity due to its structural originality. A series of 1,3-disubstituted iminobenzimidazoles was synthesized and evaluated for their in vitro cytotoxicity. The structure-activity relationship studies demonstrate that hydrophobic substituent is essential for activity. The most active compounds displayed a cytotoxicity in KB, HL60 and HCT116 human cancer cells with an IC50 of about 1μM. These first-in-class series of low molecular weight synthetic molecules may provide the basis for the development of new anticancer drugs.

Keywords: Iminobenzimidazoles, Cytotoxicity, Structure-activity relationship, Cancer, Apoptosis, Eukaryotic translation initiation factor 4F.

Article Information

Identifiers and Pagination:

Year: 2018
Volume: 12
First Page: 74
Last Page: 83
Publisher Id: TOMCJ-12-74
DOI: 10.2174/1874104501812010074

Article History:

Received Date: 20/5/2018
Revision Received Date: 8/8/2018
Acceptance Date: 12/8/2018
Electronic publication date: 31/08/2018
Collection year: 2018

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© 2018 Chouha et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this authors at the Faculty of Pharmacy, University of Strasbourg–CNRS, 67401, Illkirch, France; Tel: (+33) 368 854 141; E-mails:;


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