Effects of 2-amino-8-hydroxyquinoline interaction on the conformation of physiological isomers of human serum albumin

Abstract

The methods of synthetic chemistry create small molecules rapidly for screening, and ligand-protein interaction studies provide information on how a potential drug interacts with target or carrier proteins such as serum albumin. In this work, we investigate the interaction of amino derivative of 8-hydroxyquinoline, 2-amino-8-hydroxyquinoline (A8HQ), and the effects of its binding on the conformation of different isomers of human serum albumin (HSA) using multispectroscopic techniques and molecular modeling. We found that B isomer, which exists at pH 9, bound A8HQ (K a = 1.92 ± 0.07 × 10(5) M(-1) at 298 K) more strongly as compared with N isomer (K a = 1.19 ± 0.04 × 10(5) M(-1) at 298 K) of HSA, which is known to exist around pH 6. The binding constant at physiological pH (7.4) was also determined, and the value (K a = 1.38 ± 0.05 × 10(5) M(-1) at 298 K) was found to fall between those for N and B isomers, suggesting that both the N and B isomers exist in an equilibrium in plasma. We also determined the thermodynamic parameters such as changes in enthalpy, entropy , and free energy of binding by measuring the binding at four different temperatures. Based on molecular modeling and thermodynamic studies, we propound that the A8HQ-HSA binding involves mainly hydrophobic interactions and hydrogen bonding. Site-specific marker displacement experiments and molecular modeling showed that the molecule preferably binds in subdomain IIA close to Trp214. A8HQ binding to HSA isomers was found to cause both secondary and tertiary structural alterations in the protein.

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

“…However, 8-hydroxyquinoline favors to be docked into a pocket at an interface between domains I and II of HSA by networking with Lys106, Gln29, Tyr148, Tyr150, and Cys246 [19]. The nitro [20] and the amino [21] derivatives of 8-hydroxyquinoline prefer to form complex with serum albumin by a moderate affinity at about 10 5 M −1 binding constant. Furthermore, derivative of cloxyquin bearing iodo group at the 7 th position (5-chloro-7-iodo-8-hydroxyquinoline or clioquinol) exhibits extreme affinity toward BSA with a binding constant of 10 8 M −1 [22].…”

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

“…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 .…”