Elucidating the binding propensity of naphthyl hydroxamic acid to human serum albumin (HSA): Multi-spectroscopic and molecular modeling approach

Abstract

The association of human serum albumin (HSA) and its interaction with drug and other novel compound has garnered keen interest in designing and development for new compounds having profound pharmacokinetic and pharmacodynamic properties. In the present work, binding capacity of N-l-naphthyllaurohydroxamic acid (HAs/Compound 1) with HSA has been evaluated by novel approach involving the fluorescence photo-induced cleavage single molecule observation method. The interaction studies of the synthesized compound and HSA revealed that compound has a strong efficacy to quench the intrinsic fluorescence of HSA and the mechanism of interaction was found to be static type. UV–visible, Fluorescence spectroscopy, Synchronous spectroscopy, Fourier Transform Infrared (FT-IR) and Circular Dichroism (CD) techniques were used to confirm any alteration in the secondary structure of HSA in the presence of the compound 1. Photo-induced protein cleavage ability and molecular docking technique were also analysed in presence of HSA and compound 1. Stern-Volmer constant (Ksv), quenching constant (Kq), binding constant (Kb) and number of binding sites (n) correlating thermodynamic parameters like Gibb's free energy (ΔG), Enthalpy change (ΔH) and Entropy change (ΔS) at three temperatures viz (298, 303 or 308 K) were calculated. The molecular modeling tool was employed to ascertain the mode of interaction as well as target site on the HSA and found compound 1 interacts with sudlow site I of HSA through hydrogen bonding and hydrophobic interaction, consistent with the evaluated experimental results. CD results demonstrated that ligand interaction does not bring any conformational changes in the α-helical content of HSA. Involvement of hydroxyl radicals as the reactive species was indicated by the efficient photo-induced protein cleavage activity shown by compound 1. Thus, photo induced cleavage experiment ascertained the ability of compound 1 as a synthetic protease. These results accolade former biological studies of new specific target HAs, giving additional information about feasibility of their transport and accumulation in blood plasma.