Format

Send to

Choose Destination
J Pharm Biomed Anal. 2018 Oct 25;160:397-403. doi: 10.1016/j.jpba.2018.07.053. Epub 2018 Aug 3.

Study of the interaction of broad-spectrum antimicrobial drug sitafloxacin with human serum albumin using spectroscopic methods, molecular docking, and molecular dynamics simulation.

Author information

1
School of Chemical Engineering, Sichuan University, Chengdu 610065, China.
2
School of Chemical Engineering, Sichuan University, Chengdu 610065, China. Electronic address: tangpeixiao@126.com.
3
College of Pharmacy and Biological Engineering, Chengdu University, Chengdu 610106, China.
4
School of Chemical Engineering, Sichuan University, Chengdu 610065, China. Electronic address: lihuilab@sina.com.

Abstract

Sitafloxacin (STFX) is a new generation of broad-spectrum oral fluoroquinolones. STFX has significantly enhanced antibacterial activity than most similar drugs. Clinically, this drug is mainly used to treat respiratory and urinary tract infections and other serious bacterial infections. In this study, the interaction between sitafloxacin and human serum albumin (HSA) was investigated by spectroscopic methods and molecular simulations. Fluorescence quenching experiments showed that the interaction mechanism between STFX and HSA was static quenching, which was confirmed by time-resolved fluorescence. Thermodynamic parameters and docking results indicated that hydrophobic and electrostatic forces played a key role in this mechanism. Probe experiments and molecular docking results indicated that the major binding of STFX was at site I. 3D fluorescence showed that the insertion of STFX had minimal impact on the microenvironment. Analysis of the protein secondary structure showed that the insertion of STFX had little effect on the secondary structure of the protein. Hydrophobicity experiments showed the slight decrease in the overall hydrophobicity index of the system. Molecular dynamics simulations further validated the stability of the HSA-STFX complex. This study are useful for further drug development, in vivo toxicity studies, and can provide guidance for the clinical application of STFX to study its pharmacokinetic properties.

KEYWORDS:

Docking; Fluorescence; Human serum albumin; Molecular dynamics simulation; Sitafloxacin

PMID:
30125733
DOI:
10.1016/j.jpba.2018.07.053
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center