Understanding the interaction between α-1-acid glycoprotein (AGP) and potential Cu/Zn metallo-drugs of benzimidazole derived organic motifs: A multi-spectroscopic and molecular docking study

被引:21
|
作者
AlAjmi, Mohamed F. [1 ]
Rehman, Md Tabish [1 ]
Khan, Rais Ahmad [2 ]
Khan, Meraj A. [3 ]
Muteeb, Ghazala [4 ]
Khan, Mohd. Shahnawaz [5 ]
Noman, Omar Mohammed [6 ]
Alsalme, Ali [2 ]
Hussain, Afzal [1 ]
机构
[1] King Saud Univ, Dept Pharmacognosy, Coll Pharm, Riyadh 11451, Saudi Arabia
[2] King Saud Univ, Dept Chem, Coll Sci, Riyadh 11451, Saudi Arabia
[3] Hosp Sick Children, Program Translat Med, Peter Gilgan Ctr Res & Learning, Toronto, ON, Canada
[4] King Faisal Univ, Coll Appl Med Sci, Dept Nursing, Hofuf 400, Al Hasa 31982, Saudi Arabia
[5] King Saud Univ, Coll Sci, Dept Biochem, Prot Res Chair, Riyadh 11451, Saudi Arabia
[6] King Saud Univ, Coll Pharm, Med Aromat & Poisonous Plants Res Ctr, Riyadh 11451, Saudi Arabia
关键词
Alpha-1-acid glycoprotein (AGP); Benzimidazole-derived organic motifs; Circular dichroism; Fluorescence spectroscopy; Molecular docking; Protein-drug interaction; Schiff base ligands; HUMAN SERUM-ALBUMIN; COMPARATIVE BINDING MECHANISM; ALPHA(1)-ACID GLYCOPROTEIN; CIRCULAR-DICHROISM; CRYSTAL-STRUCTURE; FLUORESCENCE; DERIVATIVES; COMPLEXES; INHIBITORS; INSIGHT;
D O I
10.1016/j.saa.2019.117457
中图分类号
O433 [光谱学];
学科分类号
0703 ; 070302 ;
摘要
Drug-binding and interactions with plasma proteins strongly affect their efficiency of delivery, hence considered as a key factor in determining the overall pharmacological action. Alpha-1-acid glycoprotein (AGP), a second most abundant plasma protein in blood circulation, has unique drug binding ability and involved in the transportation of various compounds. Here, we have investigated the mechanism of interaction between AGP and potential Cu/Zn metallo-drugs of benzimidazole derived organic motifs (CuL2 and ZnL2, where L is Schiff base ligand) by applying integrated spectroscopic, biophysical techniques and computational molecular docking analyses. We found that both the metallo-drugs (CuL2 and ZnL2) were bound at the central cavity of AGP interacting with the residues of lobe I, lobe II as well as lobe III. The binding of metallo-drugs to AGP occurs in 1:1 M ratios. Hydrogen bonding, electrostatic and hydrophobic interactions played a significant role in stabilizing the AGP-metallo-drug complexes. Binding affinities of both the metallo-drugs towards AGP at 298 K were of the order of 10(4)-10(5) M-1, corresponding to Gibbs free energy of stabilization of approximately -5.50 to -6.62 kcal mol(-1). Furthermore, the spectroscopic investigation by circular dichroism and synchronous fluorescence analyses suggest conformational changes in AGP upon the binding of metallic compounds. (C) 2019 Elsevier B.V. All rights reserved.
引用
收藏
页数:10
相关论文
共 1 条