The understanding of the interaction between non-steroidal anti-inflammatory drugs and human serum albumin plays a fundamental role in the development of new drugs and new therapeutic strategies. Several studies have been performed, nevertheless, the interaction phenomena are still not fully understood. In this work, high-field solution Nuclear Magnetic Resonance (NMR) spectroscopy was applied to compare the strength of the interaction of diclofenac sodium salt, ketorolac tris salt and flurbiprofen sodium salt toward albumin. To this aim, mono- and bi-selective relaxation rate measurements were performed by applying selective π-pulses at the selected frequencies and by following magnetization recovery. On the basis of the dependence of relaxation parameters on albumin concentration, normalized affinity indexes were calculated for several protons of the drugs. Affinity indexes for diclofenac were about five-fold higher in comparison with ketorolac and flurbiprofen. Aromatic moieties of the three drugs and methine protons at the chiral centers of ketorolac and flurbiprofen were more involved in the interaction with albumin. In conclusion, NMR spectroscopy allows not only for the comparison of drug-to- protein affinities but also points out the nature of the drug sites that are more extensively involved in the interaction.

NMR Investigation of the Interaction of Three Non-Steroidal Anti-Inflammatory Drugs with Human Serum Albumin

Uccello-Barretta, Gloria
Secondo
;
Balzano, Federica
Ultimo
2022-01-01

Abstract

The understanding of the interaction between non-steroidal anti-inflammatory drugs and human serum albumin plays a fundamental role in the development of new drugs and new therapeutic strategies. Several studies have been performed, nevertheless, the interaction phenomena are still not fully understood. In this work, high-field solution Nuclear Magnetic Resonance (NMR) spectroscopy was applied to compare the strength of the interaction of diclofenac sodium salt, ketorolac tris salt and flurbiprofen sodium salt toward albumin. To this aim, mono- and bi-selective relaxation rate measurements were performed by applying selective π-pulses at the selected frequencies and by following magnetization recovery. On the basis of the dependence of relaxation parameters on albumin concentration, normalized affinity indexes were calculated for several protons of the drugs. Affinity indexes for diclofenac were about five-fold higher in comparison with ketorolac and flurbiprofen. Aromatic moieties of the three drugs and methine protons at the chiral centers of ketorolac and flurbiprofen were more involved in the interaction with albumin. In conclusion, NMR spectroscopy allows not only for the comparison of drug-to- protein affinities but also points out the nature of the drug sites that are more extensively involved in the interaction.
2022
Aiello, Federica; Uccello-Barretta, Gloria; Picchi, Claudio; Nazzi, Samuele; Recchimurzo, Alessandra; Balzano, Federica
File in questo prodotto:
File Dimensione Formato  
molecules-27-06647-v3.pdf

accesso aperto

Descrizione: versione dell'editore
Tipologia: Versione finale editoriale
Licenza: Creative commons
Dimensione 1.56 MB
Formato Adobe PDF
1.56 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1153952
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 7
social impact