scholarly journals Experimental and Molecular Docking Studies of Cyclic Diphenyl Phosphonates as DNA Gyrase Inhibitors for Fluoroquinolone-Resistant Pathogens

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 53
Author(s):  
Neveen M. Saleh ◽  
Yasmine S. Moemen ◽  
Sara H. Mohamed ◽  
Ghady Fathy ◽  
Abdullah A. S. Ahmed ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Dna Gyrase ◽  
Docking Study ◽  
Dna Supercoiling ◽  
Docking Studies ◽  
Clinical Isolates ◽  
Detectable Effect ◽  
Topoisomerase Iv ◽  
Molecular Docking Studies ◽  
Gyrase Inhibitors

DNA gyrase and topoisomerase IV are proven to be validated targets in the design of novel antibacterial drugs. In this study, we report the antibacterial evaluation and molecular docking studies of previously synthesized two series of cyclic diphenylphosphonates (1a–e and 2a–e) as DNA gyrase inhibitors. The synthesized compounds were screened for their activity (antibacterial and DNA gyrase inhibition) against ciprofloxacin-resistant E.coli and Klebsiella pneumoniae clinical isolates having mutations (deletion and substitution) in QRDR region of DNA gyrase. The target compound (2a) that exhibited the most potent activity against ciprofloxacin Gram-negative clinical isolates was selected to screen its inhibitory activity against DNA gyrase displayed IC50 of 12.03 µM. In addition, a docking study was performed with inhibitor (2a), to illustrate its binding mode in the active site of DNA gyrase and the results were compatible with the observed inhibitory potency. Furthermore, the docking study revealed that the binding of inhibitor (2a) to DNA gyrase is mediated and modulated by divalent Mg2+ at good binding energy (–9.08 Kcal/mol). Moreover, structure-activity relationships (SARs) demonstrated that the combination of hydrazinyl moiety in conjunction with the cyclic diphenylphosphonate based scaffold resulted in an optimized molecule that inhibited the bacterial DNA gyrase by its detectable effect in vitro on gyrase-catalyzed DNA supercoiling activity.

Novel 2-arylbenzothiazole DNA gyrase inhibitors: Synthesis, antimicrobial evaluation, QSAR and molecular docking studies

2019 ◽  
Vol 93 ◽  
pp. 103373 ◽  
Author(s):  
Iman A.Y. Ghannam ◽  
Eman A. Abd El-Meguid ◽  
Islam H. Ali ◽  
Donia H. Sheir ◽  
Ahmed M. El Kerdawy
Keyword(s):  
Molecular Docking ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Antimicrobial Evaluation ◽  
Gyrase Inhibitors

scholarly journals Molecular docking studies of gyrase inhibitors: weighing earlier screening bedrock

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
H. S. Santosh Kumar ◽  
S. Ravi Kumar ◽  
N. Naveen Kumar ◽  
S. Ajith
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Gyrase Inhibitors

scholarly journals Synthesis and Molecular Docking Studies of Coumarinyl Thiazole as Cell Division Protein Kinase 2 Inhibitor

2019 ◽  
Vol 31 (11) ◽  
pp. 2453-2456
Author(s):  
J. Brindha ◽  
T.F. Abbs Fen Reji
Keyword(s):  
Molecular Docking ◽  
Cell Division ◽  
Protein Kinase ◽  
Screening Tool ◽  
Docking Study ◽  
Docking Studies ◽  
Autodock Vina ◽  
Molecular Docking Study ◽  
Molecular Docking Studies ◽  
Cell Division Protein

A series of 2-alkylamino-4-(3-coumarinyl)thiazoles were synthesized, characterized and evaluated their anticancer activity through molecular docking studies. Cell division protein kinase 2 (PDB code: 1KE9) is selected as a target and the compounds which obeys Lipinski rule of five is selected as a ligand. Molecular docking study is carried out using AutoDock Vina in PyRx virtual screening tool. This study revealed that all the compounds are active against the molecular target and compounds 5a and 5c have the highest docking score.

scholarly journals Discovery of Novel DNA Gyrase Inhibitors by High-Throughput Virtual Screening

2007 ◽  
Vol 51 (10) ◽  
pp. 3688-3698 ◽  
Author(s):  
David A. Ostrov ◽  
José A. Hernández Prada ◽  
Patrick E. Corsino ◽  
Kathryn A. Finton ◽  
Nhan Le ◽  
...  
Keyword(s):  
Small Molecules ◽  
Dna Gyrase ◽  
Binding Pocket ◽  
Small Region ◽  
Dna Supercoiling ◽  
Resistant Bacteria ◽  
Topoisomerase Iv ◽  
Antimicrobial Drugs ◽  
Drug Resistant Bacteria ◽  
Gyrase Inhibitors

ABSTRACT The bacterial type II topoisomerases DNA gyrase and topoisomerase IV are validated targets for clinically useful quinolone antimicrobial drugs. A significant limitation to widely utilized quinolone inhibitors is the emergence of drug-resistant bacteria due to an altered DNA gyrase. To address this problem, we have used structure-based molecular docking to identify novel drug-like small molecules that target sites distinct from those targeted by quinolone inhibitors. A chemical ligand database containing approximately 140,000 small molecules (molecular weight, <500) was molecularly docked onto two sites of Escherichia coli DNA gyrase targeting (i) a previously unexplored structural pocket formed at the dimer interface of subunit A and (ii) a small region of the ATP binding pocket on subunit B overlapping the site targeted by coumarin and cyclothialidine drugs. This approach identified several small-molecule compounds that inhibited the DNA supercoiling activity of purified E. coli DNA gyrase. These compounds are structurally unrelated to previously identified gyrase inhibitors and represent potential scaffolds for the optimization of novel antibacterial agents that act on fluoroquinolone-resistant strains.

scholarly journals A Molecular Docking Study of N-Ferrocenylmethylnitroanilines as Potential Anticancer Drugs

2016 ◽  
Vol 2 ◽  
pp. 5-12 ◽  
Author(s):  
Touhami Lanez ◽  
Elhafnaoui Lanez
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
Protein Structure ◽  
Dna Gyrase ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Molegro Virtual Docker ◽  
Gyrase A

In the present study, the interaction of the protein structure of Escherichia coli DNA Gyrase-A (EcGyr-A) extracted from protein data bank (PDB Code: 1AB4) with ligands N-ferrocenylmethyl-2-nitroaniline (2FMNA), N-ferrocenylmethyl-3-nitroaniline (3FMNA) and N-ferrocenylmethyl-4-nitroaniline (4FMNA) were investigated by performing docking studies using the Molegro Virtual Docker (MVD) software. The results obtained showed that the best poses which is derived from MolDock score for Escherichia coli DNA Gyrase-A were respectively equal to-92.0111, -96.0866 and-95.6808 with reranking score equal to-40.9575, -73.4476 and-73.6423. Calculations revealed that 3FMNA react strongly with EcGyr-A followed by 4-FMNA and 2-FMNA.

Synthesis, characterization, theoretical, anti-bacterial and molecular docking studies of quinoline based chalcones as a DNA gyrase inhibitor

2014 ◽  
Vol 54 ◽  
pp. 31-37 ◽  
Author(s):  
Muhammad Imran Abdullah ◽  
Asif Mahmood ◽  
Murtaza Madni ◽  
Sara Masood ◽  
Muhammad Kashif
Keyword(s):  
Molecular Docking ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Molecular Docking Studies

Novel 1,2,4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: Design, synthesis, ADMET prediction and molecular docking study

2021 ◽  
pp. 104885
Author(s):  
Tarek S. Ibrahim ◽  
Ahmad J. Almalki ◽  
Amr H. Moustafa ◽  
Rasha M. Allam ◽  
Gamal El-Din A. Abuo-Rahma ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Dna Gyrase ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Gyrase Inhibitors
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