THE METHOD FOR DETERMINING THE ABSOLUTE CONFIGURATION USING NSUBSTITUTED CYCLIC AMINO ACIDS

Determining the absolute configuration of biologically active chiral substances is a current issue in drug development since biological properties of enantiomers may greatly vary. The absolute configuration of enantiomers can be determined using crystallography, circular dichroism, or by the method that involves chiral derivatizing agents and analysis of NMR spectra.This work was supported by the Russian Science Foundation, project no. 16-13-10358

Analysis of P‑Glycoprotein Transport Cycle Reveals a New Way to Identify Efflux Inhibitors

P-glycoprotein (P-gp) is found to be of considerable interest for the design of drugs capable of treating chemoresistant tumors. This transporter is an interesting target for which an efficient approach has not yet been developed in terms of computer simulation. In this work, we use a combination of docking, molecular dynamics, and metadynamics to fully explore the states that occur during the capture of a ligand and subsequent efflux by P-gp. The proposed approach allowed us to substantiate a number of experimentally established facts, as well as to develop a new criterion for identifying potential P-gp inhibitors

Discovery of Novel Isatin-Based p53 Inducers

A series of isatin Schiff base derivatives were identified during <i>in silico</i> screening of the small molecule library for novel activators of p53. The compounds selected based on molecular docking results were further validated by a high-content screening assay using U2OS human osteosarcoma cells with an integrated EGFP-expressing p53-dependent reporter. The hit compounds activated and stabilized p53, as shown by Western blotting, at higher rates than the well-known positive control Nutlin-3. Thus, the p53-activating compounds identified by this approach represent useful molecular probes for various cancer studies