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In silico analysis of ciprofloxacin analogs as inhibitors of DNA gyrase of Staphylococcus aureus

Authors :
Md. Rakhibul Hasan
Surid Mohammad Chowdhury
Md. Abdul Aziz
Asif Shahriar
Hossain Ahmed
Md. Arif Khan
Shafi Mahmud
Talha Bin Emran
Source :
Informatics in Medicine Unlocked, Vol 26, Iss , Pp 100748- (2021)
Publication Year :
2021
Publisher :
Elsevier, 2021.

Abstract

In this in silico study, thirty-five ciprofloxacin analogs were docked to the active site of DNA gyrase, the prime target of ciprofloxacin type antibiotics. Prior to docking all the structures were optimized using MM2 force field parameters. The study revealed that five candidates, namely 6MePQ_3, 6MePQ_11, A6MePQ_3, HPQ_11, and PQ_7, exhibited promising binding to DNA gyrase. Upon analysis of the ligand-receptor complex, it is also divulged that this binding has been stabilized by the interaction between different neutral, nonpolar, aromatic amino-acid residues of DNA gyrase and the ciprofloxacin analogs. Moreover, the interaction between ciprofloxacin analogs and DNA gyrase was mainly governed by hydrophobic interactions and, to a lesser extent, hydrogen bonds. Halogen bonds, electrostatic interactions, and other types of interactions were almost absent in all cases. Molecular dynamic simulation was performed to recognize the structural variations and the complexes' stability of suggested ligands. This study indicates that 6MePQ_3 forms a stable drug-protein complex. On the other site, Pharmacokinetic filtering done using SwissADME server, reveals that 6MePQ_3 is well absorbed from the GI tract, does not cross BBB and is not a P-gp substrate. But it is possible to check and confirm its all “in silico” pharmacodynamics and pharmacokinetics characteristics in real life by synthesis and subsequent analysis of this ligand.

Details

Language :
English
ISSN :
23529148
Volume :
26
Issue :
100748-
Database :
Directory of Open Access Journals
Journal :
Informatics in Medicine Unlocked
Publication Type :
Academic Journal
Accession number :
edsdoj.006b1cc7d68e45b2b3ab5faf89576ea3
Document Type :
article
Full Text :
https://doi.org/10.1016/j.imu.2021.100748