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

Abstract

Abstract5-Amino-8-hydroxyquinoline (5A8HQ), an amino derivative of 8-hydroxyquinoline, has become a potential anticancer candidate because of its promising proteasome inhibitory activity to overcome and yet synergize bortezomib for fighting cancers. Therefore, in this study, its physicochemical properties and interaction activities with serum protein have extensively been elucidated by both in vitro and in silico approaches to fulfill the pharmacokinetic and pharmacodynamic gaps. 5A8HQ exhibited the drug-likeness properties, where oral administration seems to be a route of choice owing to its high-water solubility and intestinal absorptivity. Multi-spectroscopic investigations suggested that 5A8HQ tended to associate with bovine serum albumin (BSA), a representative of serum protein, via the ground-state complexation. It apparently bound in a protein cleft between subdomains IIA and IIIA of BSA as suggested by the molecular docking and molecular dynamics simulations. The binding was mainly driven by hydrogen bonding and electrostatic interactions with a moderate binding constant at 104 M−1, conforming with the predicted free fraction in serum at 0.484. Therefore, 5A8HQ seems to display a good bioavailability in plasma to reach target sites and exerts its potent pharmacological activity. Likewise, serum albumin is a good candidate to be reservoir and transporter of 5A8HQ in the circulatory system.

Revealing the mechanistic interactions of profenofos and captan pesticides with serum protein via biophysical and computational investigations

“…Therefore, site I of BSA should be the predominant binding site of PF and CT. Moreover, the PC lower region is considerably bulky serving as a binding site for various molecules, such as hydroxytyrosol 42 , 5-amino-8-hydroxyquinoline 43 , and ibuprofen 44 . Also, the PC lower region of BSA could potentially serve as a binding pocket for PF and CT, particularly under saturated conditions.…”