The 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl Phthalimide Derivatives as Prodrugs-Spectroscopic and Theoretical Binding Studies with Plasma Proteins

Int J Mol Sci. 2022 Jun 23;23(13):7003. doi: 10.3390/ijms23137003.

Abstract

Many publications in databases deal with the interactions of new drugs with albumin. However, it is not only albumin that is responsible for binding pharmaceutical molecules to proteins in the human body. There are many more proteins in plasma that are important for the study of the ADME pathway. Therefore, in this study, we have shown the results of the interactions between the plasma proteins albumin, orosomucoid, and gamma globulins and non-toxic anti-inflammatory phthalimide analogs, which due to the promising obtained results, may be potential candidates in the group of analgesic and anti-inflammatory drugs. Using spectroscopic methods and molecular modeling, we showed that all four tested compounds form complexes with the analyzed proteins. The formation of a complex with proteins raises the pharmacological efficacy of the drug. Therefore, the obtained results could be a step in the study of the pharmacokinetics and pharmacodynamics of new potential pharmaceuticals.

Keywords: molecular docking; phthalimide analogs; phthalimide derivatives; plasma proteins; spectroscopic methods.

MeSH terms

  • Albumins
  • Analgesics
  • Humans
  • Molecular Docking Simulation
  • Orosomucoid / metabolism
  • Phthalimides / chemistry
  • Phthalimides / pharmacology
  • Prodrugs* / pharmacology

Substances

  • Albumins
  • Analgesics
  • Orosomucoid
  • Phthalimides
  • Prodrugs

Grants and funding

This research received no external funding. Only the nitrogen gas to CD spectroscopy studies was funded by Wroclaw Medical University, grant number SUBZ.DO80.22.024.