Evaluation of in silico ADMET analysis and human serum albumin interactions of a new lanthanum(III) complex by spectroscopic and molecular modeling studies

• Published in: Inorganica Chimica Acta 2017-07, Vol.463, p.80-87
• Main Authors: Shahraki, Somaye, Shiri, Fereshteh, Saeidifar, Maryam
• Format: Article
• Language: English
• Subjects: Binding sites; Chemical compounds; Computer simulation; Drugs; Fluorescence; Human serum albumin; Hydrogen bonds; Hydrophobic surfaces; In silico ADMET; Infrared radiation; Interaction; Lanthanum; Lanthanum(III) complex; Molecular chains; Molecular docking; Molecular structure; NMR; Nuclear magnetic resonance; Parameters; Phenylalanine; Proteins; Quenching; Serum albumin; Spectroscopic analysis; Spectrum analysis
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/j.ica.2017.04.023

In this study a new lanthanum(III) complex with phenylalanine was synthesized. The interaction of this complex with human serum albumin using spectroscopic and molecular docking techniques was investigated. [Display omitted] •A new lanthanum(III) complex with phenylalanine amino acid was synthesized.•Toxicity risk assessment test showed that there is no toxicity for lanthanum(III) complex.•Experimental results suggest that La(III) complex interacted with HSA by hydrogen bonding and hydrophobic forces.•Molecular docking indicated that lanthanum(III) complex is embedded into subdomain IB of protein. A new lanthanum(III) complex, [La(Phe)3(H2O)2] (Phe=phenylalanine), was synthesized. The complex was characterized by elemental analysis, conductivity measurement, FT-IR, UV/Vis and 1H NMR techniques. Drug-like properties of this complex was evaluated through in silico ADMET predictions. The reactivity of this complex to human serum albumin (HSA) under simulated physiological conditions was studied by spectroscopic and molecular docking analysis. The fluorescence quenching of protein by addition of La(III) complex was due to static quenching mechanism. The thermodynamic parameters show that the binding process was spontaneous and that hydrogen bonds and hydrophobic forces play a major role in the association of the HSA–La(III) complex. Binding parameters between La(III) complex and protein such as binding sites number (n ∼1) and binding constant (Ka ∼104M−1) were determined. The conformational changes of protein secondary structure in the presence of above complex were demonstrated by FT-IR, three-dimensional fluorescence and UV–Vis absorption techniques. Molecular docking of La(III) complex relating to HSA was investigated and confirmed the experimental results. All these experimental and computational results clarified that La(III) complex could bind with HSA effectively, which could be a useful guideline for efficient drug design.