Hybrid Isoxazole-Hydroxyapatite composites as antimicrobial agents: integrated in silico and in vitro investigation

In this study, an innovative methodology was implemented to combine an isoxazole derivative (ARZ) with hydroxyapatite (HAp), varying several parameters to obtain three distinct composites (ARZ-Hap-1, ARZ-Hap-2 and ARZ-Hap-3). These composites (ARZ-Hap) were synthesized by a dissolution-recrystallization process, thereby facilitating enhanced interaction between ARZ and HAp. This approach promoted homogeneous dispersion of ARZ within the HAp matrix, consequently enhancing the stability and functionality of the resulting materials. The structural characterization of these composites was determined by FT-IR, XRD, BET, TGA, and NMR (¹³C, ³¹P) methods. Subsequently, the composites were subjected to a rigorous evaluation process to ascertain their antibacterial and antifungal activities. Among them, ARZ-HAp-3 exhibited noticeable antimicrobial activity against E. coli, S. aureus, and B. subtilis, demonstrating a measurable inhibitory effect on bacterial growth. In terms of antifungal activity, this composite demonstrated the best results, particularly against C. albicans and F. oxysporum, with minimal MIC and MFC values comparable to those of fluconazole. These results indicate the potential of the ARZ-HAp-3 composite as a promising bioactive material, demonstrating a combination of structural efficiency and targeted biological activity. The release of ARZ from the composites was monitored by UV-Visible spectroscopy, revealing a gradual and controlled profile. The quantity of the substance released is proportional to the initial content of ARZ, with a maximum observed for ARZ-Hap-3 (~900 mg/L). This mechanism, based on slow diffusion, confirms the potential of these materials for sustained release of active ingredients. Furthermore, a molecular docking analysis was conducted to explore potential interactions between ARZ and biological targets associated with the pathogens studied. The results of the study indicated a high binding affinity of ARZ with certain enzymes that are essential for bacterial and fungal survival. This finding corroborates the experimental observations made in the study, thereby providing a scientific rationale for the observed effects.