Binding mechanism, photo-induced cleavage and computational studies of interaction cefepime drug with Human serum albumin.

Abstract

The binding interaction of cefepime to human serum albumin (HSA) in aqueous solution was investigated by molecular spectroscopy (UV spectra, fluorescence spectra and CD spectra), photo-cleavage and modeling studies under simulative physiological conditions. Spectrophotometric results are rationalized in terms of a static quenching process and binding constant (K_b) and the number of binding sites (n ≈ 1) were calculated using fluorescence quenching approaches at three temperature settings. Thermodynamic data of ΔG, ΔH and ΔS at different temperatures were evaluated. The results showed that the electrostatic and hydrogen bonding interactions play a major role in the binding of cefepime to HSA. The value of 3.4 nm for the distance r between the donor (HSA) and acceptor (cefepime) was derived from the fluorescence resonance energy transfer (FRET). FTIR and CD measurements has been reaffirmed HSA-cefepime association and demonstrated reduction in α-helical content of HSA. Furthermore, the study of molecular modeling also indicated that cefepime could strongly bind to the site I (subdomain IIA) of HSA. Additionally, cefepime shows efficient photo- cleavage of HSA cleavage. Our results may provide valuable information to understand the pharmacological profile of cefepime drug delivery in blood stream.