นโยบายงานวิจัย /จรรยาบรรณนักวิจัย /ระดับคุณภาพบทความวิจัยตีพิมพ์ /ระดับคุณภาพผลงานวิชาการ /แหล่งทุน /ดาวน์โหลด /ฐานข้อมูลวิจัย /วิเคราะห์-สังเคราะห์งานวิจัย /ลิขสิทธิ์ /ข่าว


Discovery of 4-Aminoquinoline Derivatives as Novel Mycobacterium tuberculosis DNA gyraseB Inhibitors: Molecular Docking Calculations and Molecular Dynamic Simulations 


Author

-

บัณฑิต คำศรี และคณะ


Journal

- การประชุม มอบ.วิจัย ครั้งที่ 12 มหาวิทยาลัยอุบลราชธานี

Volume

- 12

Year

- 2018

Publication type

-

Page list

- 146-155

Abstract

   

4-aminoquinoline derivatives is fluoroquinolone line drug, that use as M. tuberculosis DNA gyraseB inhibitor, that is the causative agent of tuberculosis. Molecular docking calculations have been applied to elucidate the crucial interactions. The validation of the Autodock 4.2 program was determined by comparison of the docked ligand and ligand x-ray of the DNA gyraseB inhibitor.  RMSD value with 1 angstrom, which making it possible to confirm that the molecular docking calculations used are reliable. The crucial interactions of 4-aminoquinoline derivatives in DNA gyraseB binding pocket were found hydrogen bonding interactions with Asn72 and Val118 residues and pi-cation interaction with Arg433 residue. In addition, molecular dynamic simulations was performed in order to inhibit the enzyme activity of DNA gyraseB. Molecular dynamic simulations make it possible to understand the crucial interaction with the gyraseB DNA. The crucial interactions of 4-aminoquinoline derivatives in DNA gyraseB binding pocket were found hydrogen bonding interactions with Glu41, Gly76 and Met93 residues and pi-cation interaction with ARG75 and ARG433 residues. Therefore, the obtained results aid to better understanding of structural basis  4-aminoquinoline derivatives for rational design with more potent DNA gyraseB inhibitors as potential anti-tuberculosis agents.  
 


Keywords

   

 4-aminoquinoline, DNA gyraseB, M. Tuberculosis, Molecular Docking Calculations,             Molecular Dynamic Simulations