Author/Authors :
Chouha, Nora Laboratory of Therapeutic Innovation (UMR 7200) - Faculty of Pharmacy - University of Strasbourg–CNRS, 67401, Illkirch, France , Hammoud, Hassan Laboratory of Therapeutic Innovation (UMR 7200) - Faculty of Pharmacy - University of Strasbourg–CNRS, 67401, Illkirch, France , Brogi, Simone European Research Centre for Drug Discovery (Nat SynDrugs) - Department of Biotechnology - Chemistry and Pharmacy (DBCF) - University of Siena, Siena, Italy , Campiani, Giuseppe European Research Centre for Drug Discovery (Nat SynDrugs) - Department of Biotechnology - Chemistry and Pharmacy (DBCF) - University of Siena, Siena, Italy , Welsch, Caroline INSERM U981 - Gustave Roussy Cancer Campus, Villejuif, France , Robert, Caroline INSERM U981 - Gustave Roussy Cancer Campus, Villejuif, France , Vagner, Stéphan Institut Curie - PSL Research University, CNRS UMR3348,91405, Orsay, France , Cresteil, Thierry IPSIT - Faculty of Pharmacy - Université Paris-Sud, 92290 Chatenay-Malabry, France , Bentouhami, Embarek Laboratory of Therapeutic Innovation (UMR 7200) - Faculty of Pharmacy - University of Strasbourg–CNRS, 67401, Illkirch, France , Désaubry, Laurent Laboratory of Therapeutic Innovation (UMR 7200) - Faculty of Pharmacy - University of Strasbourg–CNRS, 67401, Illkirch, France
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.
Keywords :
Iminobenzimidazoles , Cytotoxicity , Structure-activity relationship , Cancer , Apoptosis , Eukaryotic translation initiation factor 4F
