Synthesis of a Novel Fluoroquinolone and Its Interaction with Human Serum Albumin: Thermodynamic Parameters and Changes in the Secondary Structure of the Protein

Abstract Objective: A novel fluoroquinolone (PFQA) with biological activity was developed and obtained via a four-step synthesis. This study aimed to characterize its interaction with human serum albumin (HSA) and compare its binding efficiency and mechanism with other representatives of the fluoroquinolone class. Methods: The compound of interest was obtained by a four-step synthesis. Spectroscopic methods (fluorescence, FTIR, CD, etc.) were utilized to investigate PFQA complex formation with HSA. Results and Discussion: PFQA demonstrates moderate binding affinity to human serum albumin (Kbinding = 3 × 102 M–1) at site II (subdomain IIIA), as shown by fluorescence spectroscopy. According to thermodynamic parameters, the new compound forms a complex with the protein primarily through hydrophobic interactions. The introduction of a bulky hydrophobic substituent at position 3 of the fluoroquinolone does not cause significant conformational changes in albumin. The obtained results were compared with data for known representatives of fluoroquinolones of different generations in terms of the most important physicochemical and biological properties that must be considered for the design of new drug molecules. Conclusions: The characteristics obtained for PFQA correspond to the parameters of the fluoroquinolones used, suggesting similar pharmacokinetic parameters in vivo.