This study presents a novel and comprehensive analysis of the interactions between newly synthesized quinoline derivatives (QDs: QuiC3H7, QuiC7H7, QuiC6H5, QuiC8H9) with potential therapeutic activity and human serum albumin (HSA). QDs have never been synthesized or studied before, therefore the obtained results constitute a novel achievement. To obtain the goals, spectroscopic and calorimetric techniques were used. Initially, in silico analysis was used to determine the most important physicochemical and pharmacokinetic properties of QDs. All compounds showed also the ability to absorb UV–Vis radiation and exhibited both π-π* and n-π* electronic transitions. Their antioxidant activity was analyzed using DPPH and ABTS assays and it can be described as follows: QuiC7H7 = QuiC8H9 < QuiC3H7 < QuiC6H5. Calorimetric analysis showed that the he affinity of HSA towards all applied QDs was moderate, and HSA exhibited the highest affinity for QuiC7H7. All analyzed reactions were spontaneous (∆G < 0, ∆S > 0), exothermic (∆H < 0) and ionic bonds were the predominant non-covalent interactions in analyzed ligand–protein complexes. All QDs could interact with HSA at both high-affinity binding sites, but none of them bound predominantly to binding sites I or II. The mean percentage of displacement of dansylated amino acids (dGlu, dPro) from the HSA molecule by QDs were in the range of 15% to 34%. None of the included ligands caused a significant chance in the percentage of α-helix in the HSA molecule, while almost all QDs caused significant changes the near-UV CD spectrum, particularly in Region 1st, Region 2nd, Region 3rd. QuiC3H7 and QuiC7H7 induced conformational changes in the environment of all aromatic amino acid residues, including the tryptophan residue at position 214 (Trp-214). It confirmed that they probably interact with HSA at Sudlow site I. In contrast, QuiC8H9 did not induce changes in the Region 3rd of the HSA spectrum. It suggests that this compound can probably bind to the HSA in the regions different than binding site I. The analysis of near-UV CD spectra allowed for the identification of high-affinity binding sites for the included QDs.

Spectroscopic and calorimetric analysis of the interaction between human serum albumin and newly synthesized quinoline derivatives

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发表日期：

2026年4月18日

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Wojciech Rogóż,
Aleksandra Owczarzy,
Karolina Kulig,
Andrzej Zięba,
Małgorzata Maciążek-Jurczyk

摘要

This study presents a novel and comprehensive analysis of the interactions between newly synthesized quinoline derivatives (QDs: QuiC₃H₇, QuiC₇H₇, QuiC₆H₅, QuiC₈H₉) with potential therapeutic activity and human serum albumin (HSA). QDs have never been synthesized or studied before, therefore the obtained results constitute a novel achievement. To obtain the goals, spectroscopic and calorimetric techniques were used. Initially, in silico analysis was used to determine the most important physicochemical and pharmacokinetic properties of QDs. All compounds showed also the ability to absorb UV–Vis radiation and exhibited both π-π* and n-π* electronic transitions. Their antioxidant activity was analyzed using DPPH and ABTS assays and it can be described as follows: QuiC₇H₇ = QuiC₈H₉ < QuiC₃H₇ < QuiC₆H₅. Calorimetric analysis showed that the he affinity of HSA towards all applied QDs was moderate, and HSA exhibited the highest affinity for QuiC₇H₇. All analyzed reactions were spontaneous (∆G < 0, ∆S > 0), exothermic (∆H < 0) and ionic bonds were the predominant non-covalent interactions in analyzed ligand–protein complexes. All QDs could interact with HSA at both high-affinity binding sites, but none of them bound predominantly to binding sites I or II. The mean percentage of displacement of dansylated amino acids (dGlu, dPro) from the HSA molecule by QDs were in the range of 15% to 34%. None of the included ligands caused a significant chance in the percentage of α-helix in the HSA molecule, while almost all QDs caused significant changes the near-UV CD spectrum, particularly in Region 1st, Region 2nd, Region 3rd. QuiC₃H₇ and QuiC₇H₇ induced conformational changes in the environment of all aromatic amino acid residues, including the tryptophan residue at position 214 (Trp-214). It confirmed that they probably interact with HSA at Sudlow site I. In contrast, QuiC₈H₉ did not induce changes in the Region 3rd of the HSA spectrum. It suggests that this compound can probably bind to the HSA in the regions different than binding site I. The analysis of near-UV CD spectra allowed for the identification of high-affinity binding sites for the included QDs.