Supercritical fluid chromatography for separation of chiral planar metallocenes.

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.

Fluorocyclopropane-Containing Proline Analogue: Synthesis and Conformation of an Item in the Peptide Chemist's Toolbox.

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.

Drug Repurposing: Deferasirox Inhibits the Anti-Apoptotic Activity of Mcl-1.

Introduction: 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.

Binding mode of Pyridoclax to myeloid cell leukemia-1 (Mcl-1) revealed by nuclear magnetic resonance spectroscopy, docking and molecular dynamics approaches.

Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 family proteins. Its amplification is one of the most frequent genetic aberrations found in human cancers. Pyridoclax, a promising BH3 mimetic inhibitor, interacts directly with Mcl-1 and induces massive apoptosis at a concentration of 15 µM in combination with anti-Bcl-x strategies in chemo-resistant ovarian cancer cell lines.

Rational design of carbamate-based dual binding site and central AChE inhibitors by a "biooxidisable" prodrug approach: Synthesis, in vitro evaluation and docking studies.

Herein, we report a new class of dual binding site AChE inhibitor 4 designed to exert a central cholinergic activation thanks to a redox-activation step of a prodrug precursor 3. Starting from potent pseudo-irreversible quinolinium salts AChE inhibitors 2 previously reported, a new set of diversely substituted quinolinium salts 2a-p was prepared and assayed for their inhibitory activity against AChE. Structure-activity relationship (SAR) analysis of 2a-p coupled with molecular docking studies allowed us to determine which position of the quinolinium scaffold may be considered to anchor the phtalimide fragment presumed to interact with the peripheral anionic site (PAS).