Abstract
Ceftazidime is a well-known cephalosporin antibiotic included in the World Health Organization's list of essential medicines. Herein, we investigated the molecular interactions of ceftazidime with bovine serum albumin (BSA) using detailed steady-state fluorescence spectroscopy supported by ultraviolet–visible and circular dichroism spectroscopies together with comprehensive molecular docking and density functional theory analyses. The formation of complex between ceftazidime and BSA was confirmed by the changes observed in the electronic spectra of BSA in the absence and presence of the drug. In particular, ceftazidime quenched the fluorescence emission of BSA and the inner filter effect was also corrected before the data analysis, as it significantly affected the fluorescence quenching. Moreover, the static quenching mechanism was proved to be involved in the 1:1 binding between BSA and ceftazidime, and ceftazidime partially unfolded the protein. Based on the experimental data, the interaction was mainly due to hydrophobic interactions, and molecular docking analysis revealed that other forces, such as hydrogen bonding and van der Waals, were also involved in the interaction. The primary binding site of ceftazidime in BSA was the interfacial region of the three domains with the maximum participation of domain 1. Frontier molecular orbital calculations demonstrated that the complexed ceftazidime was more stable than the free state, implying the formation of a stable complex with BSA, which was also consistent with the spontaneity of the experimentally identified interactions.
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•There was 1:1 binding between BSA and ceftazidime which has taken place via static quenching mechanism.•Hydrophobic forces along with hydrogen bonding and Van der Waals forces were involved in the binding.•There was a small change in the secondary structure of BSA.•The principal binding site of ceftazidime was at interfacial region of all three domains.