5 research outputs found
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