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Asma Bourafai-Aziez,1 Mohammed Benabderrahmane,2 Hippolyte Paysant,3,4 Louis-Bastien Weiswald,3,4 Laurent Poulain,3,4 Ludovic Carlier,5 Delphine Ravault,5 Marie Jouanne,2 Gaël Coadou,1 Hassan Oulyadi,1 Anne-Sophie Voisin-Chiret,2 Jana Sopková-de Oliveira Santos,2 Muriel Sebban1 1Normandie Université, UNIROUEN, INSA de Rouen, CNRS Laboratoire COBRA (UMR 6014 & FR 3038), Rouen, 76000, France; 2Normandie Univ, UNICAEN, CERMN, Caen, 14000, France; 3Normandie Université, UNICAEN, Inserm U1086 ANTICIPE «Interdisciplinary Research Unit for Cancer Prevention and Treatment», Biology and Innovative Therapeutics for Ovarian Cancers Group (BioTICLA), Centre de Lutte Contre le Cancer F. Baclesse, Caen, 14076, France; 4UNICANCER, Centre de Lutte Contre le Cancer F. Baclesse, Caen, 14076, France; 5Sorbonne Université, École Normale Supérieure, PSL University, CNRS, Laboratoire des Biomolécules, LBM, Paris, FranceCorrespondence: Muriel SebbanNormandie Université, UNIROUEN, INSA de Rouen, CNRS Laboratoire COBRA (UMR 6014 & FR 3038), Rouen, 76000, France, Tel +33 2 35 52 29 44Fax +33 2 35 52 24 41Email muriel.sebban@univ-rouen.frJana Sopková-de Oliveira SantosNormandie Univ, UNICAEN, CERMN, Caen, 14000, FranceTel +33 2 31 56 68 21Fax +33 2 31 56 68 03Email jana.sopkova@unicaen.frIntroduction: With the aim of repositioning commercially available drugs for the inhibition of the anti-apoptotic myeloid cell leukemia protein, Mcl-1, implied in various cancers, five molecules, highlighted from a published theoretical screening, were selected to experimentally validate their affinity toward Mcl-1.Results: A detailed NMR study revealed that only two of the five tested drugs, Torsemide and Deferasirox, interacted with Mcl-1. NMR data analysis allowed the complete characterization of the binding mode of both drugs to Mcl-1, including the estimation of their affinity for Mcl-1. Biological assays evidenced that the biological activity of Torsemide was lower as compared to the Deferasirox, which was able to efficiently and selectively inhibit the anti-apoptotic activity of Mcl-1. Finally, docking and molecular dynamics led to a 3D model for the Deferasirox:Mcl-1 complex and revealed the positioning of the drug in the Mcl-1 P2/P3 pockets as well as almost all synthetic Mcl-1 inhibitors. Interestingly, contrary to known synthetic Mcl-1 inhibitors which interact through Arg263, Deferasirox, establishes a salt bridge with Lys234.Conclusion: Deferasirox could be a potential candidate for drug repositioning as Mcl-1 inhibitor.Keywords: drug repurposing, Mcl-1, Deferasirox, NMR, docking, dynamics

Unsymmetrically disubstituted metallocene derivatives, characterized as the first sandwich structure, have found interest in asymmetrical synthesis and in medicinal chemistry as well. Besides, they present a particular case of chirality. Twenty original and six commercially available molecules presenting either i) a planar chirality or ii) an asymmetrical carbon containing group or iii) being symmetrically substituted were analyzed in supercritical fluid chromatography on eleven polysaccharide-based chiral stationary phases with carbon dioxide containing 30% of methanol or 2-propanol as a co-solvent mobile phase. A basic additive, either diethylamine, triethylamine or n-butylamine was also required at 1% to the co-solvent for elution. While some of the tested chiral stationary phases provided enantioseparation for the racemates, chlorinated cellulosic phases proved to be both highly retentive and highly enantioselective towards these particular species with the highest rate of success compared to their non-chlorinated counterparts. For instance, the resolution value was equal to 14.1 for one ferrocene derivative in one-hour analysis time on cellulose tris(3,5-dichlorophenylcarbamate) column with 30% 2-propanol/1% n-butylamine while a single peak was observed under the same conditions on cellulose tris(3,5-dimethylphenylcarbamate) column. Experimental parameters were arbitrarily set at 150 bar outlet pressure, 40 °C temperature and 3 mL/min flow-rate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Over the years, numerous modifications to the structure of proline have been made in order to tune its effects on bioactive compounds. Notably, the introduction of a cyclopropane ring or a fluorine atom has produced interesting results. Herein, we describe the synthesis of a proline containing fluorocyclopropane. This modified amino acid was inserted into a tripeptide, whose conformation was studied by nuclear magnetic resonance and density functional theory calculations., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)