Human serum albumin (HSA) is an abundant plasma protein, which attracts great interest in the pharmaceutical industry since it can bind a remarkable variety of drugs impacting their delivery and efficacy and ultimately altering the drug’s pharmacokinetic and pharmacodynamic properties. Additionally, HSA is widely used in clinical settings as a drug delivery system due to its potential for improving targeting while decreasing the side effects of drugs. It is thus of great importance from the viewpoint of pharmaceutical sciences to clarify the structure, function, and properties of HSA–drug complexes. This review will succinctly outline the properties of binding site of drugs in IIA subdomain within the structure of HSA. We will also give an overview on the binding characterization of interactive association of drugs to human serum albumin that may potentially lead to significant clinical applications.

Mononuclear and trinuclear zinc(II) complexes (1 and 2) with tridentate NNO Schiff-base ligands (HL¹ = N-2-pyridiylmethylidene-4-chloro-2-hydroxy-phenylamine, HL² = N-2-pyridiylmethylidene-2-hydroxy-5-chloro-phenylamine) have been synthesized and characterized by single-crystal X-ray diffraction and elemental analysis. The binding properties of zinc(II) complexes with calf thymus DNA (CT-DNA) and HSA were investigated by UV–visible, fluorescence, and circular dichroism spectra. The zinc(II) complexes bind significantly to CT-DNA by intercalation and bind to protein HSA through a static quenching mechanism. The in vitro cytotoxicity of the complexes on human tumor cells lines was assessed by 3-(4,5-dimathylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide, Hoechst 33258 staining experiments. Graphical Abstract