Keywords
Abstract
The aim of the study – to research the interactions of propoxazepam and some 1,4-benzodiazepine derivatives with human serum albumin by molecular docking and analysis of the components of these interactions.
Molecular docking was carried out using the iGEMDOCK v 2.1 program, albumin structures (with diazepam (2BXF) and ibuprofen (2BXG)) were obtained from a database of biological macromolecules (http://www.rcsb.org/). Structures of ligands (diazepam, oxazepam, propoxazepam, 3-hydroxypropoxazepam,
ibuprofen) were optimized for internal energy in Avogadro (v 1.2.0) and presented in *.pdb format. Visualization of docking results was carried out using the ezCADD resource.
The compounds show cross-affinity for binding sites, but are more prone to interact with the benzodiazepine binding site, while the binding energy of propoxazepam (– 10.27 kcal/mol) is the highest among the studied structures and even exceeds this indicator for diazepam. The binding characteristics calculated in the process of molecular docking correspond to the real ones, but with a partial overestimation of the data for the diazepam site.
According to the results of molecular docking to the diazepam and ibuprofen binding sites of human serum albumin with the reference compounds – diazepam and ibuprofen, it was found that the compounds show cross-relatedness to the binding sites, although diazepam shows a higher interaction energy (– 9.38 kcal/mol) with its own site than with ibuprofen’s (– 7.32 kcal/mol).
The energy of binding to the diazepam site for propoxazepam (– 10.27 kcal/mol) is the highest among the studied structures and even exceeds this indicator for diazepam, and its position differs in the formation of bonds with the bromine atom (position «7»), in contrast to diazepam, which interacts through the
oxygen of the carbonyl group of the hetero ring. At the ibuprofen binding site, propoxazepam clearly interacts with a different site, but with common amino acid residues.