Insight into the Molecular Interaction of Cloxyquin (5-chloro-8-hydroxyquinoline) with Bovine Serum Albumin: Biophysical Analysis and Computational Simulation

Abstract

Cloxyquin is a potential therapeutic compound possessing various bioactivities, especially antibacterial, antifungal, cardioprotective, and pain relief activities. Herein, the interaction mechanism between cloxyquin and bovine serum albumin (BSA) has been elucidated in order to fulfill its pharmacokinetic and pharmacodynamic gaps essential for further development as a therapeutic drug. Multi-spectroscopic and biophysical model analysis suggested that cloxyquin interacts with BSA via a static process by ground-state complex formation. Its binding behavior emerged as a biphasic fashion with a moderate binding constant at the level of 104 M−1. Thermodynamic analysis and molecular docking simulation concurrently revealed that hydrophobic interaction is a major driving force for BSA–cloxyquin complexation. Binding of cloxyquin tends to slightly enlarge the monomeric size of BSA without a significant increase of aggregate fraction. Cloxyquin preferentially binds into the fatty acid binding site 5 (FA5) of the BSA via hydrophobic interaction amongst its quinoline scaffold and Phe550, Leu531, and Leu574 residues of BSA. The quinoline ring and hydroxyl moiety of cloxyquin also form the π–π interaction and the hydrogen bond with Phe506. Our data indicate a potential function of serum albumin as a carrier of cloxyquin in blood circulation.

Liposomal Formulations of a New Zinc(II) Complex Exhibiting High Therapeutic Potential in a Murine Colon Cancer Model

“…In both cases, one binding site was obtained, with n = 0.91 and 1.04 for [ZnL(AcO)] and [ZnL 2 ], respectively. These results are in good agreement with previously published data for 8-hydroxyquinoline derivatives [ 45 ] and other metal complexes bearing hydrazone ligands [ 46 ]. Association constants in the range of 10 4 –10 5 M −1 are considered to represent moderate to strong binders, which indicates that the complexes can be transported in the serum by the protein [ 47 ] and released at the target site.…”

In silico and multi-spectroscopic analyses on the interaction of 5-amino-8-hydroxyquinoline and bovine serum albumin as a potential anticancer agent

“…Besides, hydrophobic interaction was observed between quinoline ring of 5A8HQ and hydrophobic side chains of Leu197 and Leu480. These findings were well-concurrent with previous reports, showing that the PC lower pocket of BSA was a preferred binding site for 8HQ derivatives, i.e., 8HQ 57 , cloxyquin 50 , and clioquinol 58 .

Figure 9 ( A ) Ribbon representation of BSA structure and superimposition of 5A8HQ (yellow surface contour) at the most favorable binding site.

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“…In the presence of 5A8HQ (Fig. 6 B), intensity of peak A was slightly increased, implying that 5A8HQ induces hydrodynamic diameter enlargement of the BSA that in turn enhances the Rayleigh scattering effect 49 – 51 as previously observed on other 8HQ derivatives 50 . In addition, 5A8HQ apparently induced intensity losses of peak B and peak C, suggesting that it exerts direct effects on BSA conformation by inducing polypeptide chain alterations and microenvironmental changes around the Trp and Tyr residues.…”

“…5A8HQ possessed drug-likeness properties with high water solubility and intestinal absorptivity. Fluorescence quenching studies indicated that 5A8HQ was associated with BSA through the ground-state complex formation with a moderate binding constant at 10 4 M −1 , which was comparable to other 8HQ derivatives, such as 2‑amino‑8‑hydroxyquinoline 62 and 5-chloro-8-hydroxyquinoline 50 , but not clioquinol (5-chloro-7-iodo-8-hydroxyquinoline; = 10 8 M −1 ) 58 . However, in vitro obtained binding constant is a preliminary information, which may need further exploration in vivo because some endogenous factors can exert synergistically or antagonistically effect on the binding affinity 63 .…”

Investigating binding dynamics of trans resveratrol to HSA for an efficient displacement of aflatoxin B1 using spectroscopy and molecular simulation

“…2 a, it is clear that in the presence of an increasing concentration of trans -resveratrol, the hyperchromic effect was observed at absorption maxima (λ max ) of HSA, coupled with bathochromic shift, suggesting structural alterations in the native structure of HSA and a ground state complex formation between trans -resveratrol and HSA 20 . The absorption spectrum also gives a clue about the existence of static quenching between trans -resveratrol and HSA, since in static type of quenching, the absorption spectra of native protein changes in the presence of a ligand molecule, however in dynamic quenching, it remains unaffected 21 , 22 . Fluorescence spectroscopy was performed to get insight into the binding and thermodynamics parameters associated with the interaction of trans -resveratrol with HSA.…”