LETTER
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, *
Article Information
Identifiers and Pagination:
Year: 2018Volume: 12
First Page: 74
Last Page: 83
Publisher ID: TOMCJ-12-74
DOI: 10.2174/1874104501812010074
Article History:
Received Date: 20/5/2018Revision Received Date: 8/8/2018
Acceptance Date: 12/8/2018
Electronic publication date: 31/08/2018
Collection year: 2018
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: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.
