Here, we have identified the interaction site of the contraceptive drug gamendazole using computational modeling. The drug was previously described as a ligand for eukaryotic translation elongation factor 1-α 1 (eEF1A1) and found to be a potential target site for derivatives of 2-phenyl-3-hydroxy-4(1 H)-quinolinones (3-HQs), which exhibit anticancer activity. The interaction of this class of derivatives of 3-HQs with eEF1A1 inside cancer cells was confirmed via pull-down assay. We designed and synthesized a new family of 3-HQs and subsequently applied isothermal titration calorimetry to show that these compounds strongly bind to eEF1A1. Further, we found that some of these derivatives possess significant in vitro anticancer activity.

Department of Biophysics 2nd Faculty of Medicine Charles University 5 Úvalu 84 150 06 Praha 5 Czech Republic Department of Tissue Engineering The Czech Academy of Sciences Institute of Experimental Medicine Vídeňská 1083 142 20 Praha 4 Czech Republic University Center for Energy Efficient Buildings The Czech Technical University Prague Třinecká 1024 273 43 Bustehrad Czech Republic

Department of Medical Chemistry and Clinical Biochemistry 2nd Faculty of Medicine Charles University and Motol University Hospital 5 Úvalu 84 150 06 Praha 5 Czech Republic Department of Tissue Engineering The Czech Academy of Sciences Institute of Experimental Medicine Vídeňská 1083 142 20 Praha 4 Czech Republic

Department of Organic Chemistry Faculty of Science Palacký University Tř 17 listopadu 12 771 46 Olomouc Czech Republic

Institute of Molecular and Translation Medicine Faculty of Medicine and Dentistry Palacký University Hněvotínská 5 779 00 Olomouc Czech Republic

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$a Identification of Eukaryotic Translation Elongation Factor 1-α 1 Gamendazole-Binding Site for Binding of 3-Hydroxy-4(1 H)-quinolinones as Novel Ligands with Anticancer Activity / $c K. Burglová, G. Rylová, A. Markos, H. Prichystalova, M. Soural, M. Petracek, M. Medvedikova, G. Tejral, B. Sopko, P. Hradil, P. Dzubak, M. Hajduch, J. Hlavac,

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$a Here, we have identified the interaction site of the contraceptive drug gamendazole using computational modeling. The drug was previously described as a ligand for eukaryotic translation elongation factor 1-α 1 (eEF1A1) and found to be a potential target site for derivatives of 2-phenyl-3-hydroxy-4(1 H)-quinolinones (3-HQs), which exhibit anticancer activity. The interaction of this class of derivatives of 3-HQs with eEF1A1 inside cancer cells was confirmed via pull-down assay. We designed and synthesized a new family of 3-HQs and subsequently applied isothermal titration calorimetry to show that these compounds strongly bind to eEF1A1. Further, we found that some of these derivatives possess significant in vitro anticancer activity.

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