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.
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