Esterprodrugs of ciprofloxacin as DNA-gyrase inhibitors: synthesis, antiparasitic evaluation and docking studies

MedChemComm ◽  
2011 ◽  
Vol 2 (5) ◽  
pp. 430-435 ◽  
Author(s):  
Faustine Dubar ◽  
René Wintjens ◽  
Érica S. Martins-Duarte ◽  
Rossiane C. Vommaro ◽  
Wanderley de Souza ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Modeling ◽  
Toxoplasma Gondii ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Mechanisms Of Action ◽  
Computational Calculations ◽  
Gyrase Inhibitors ◽  
Ester Prodrugs

Novel ester prodrugs of ciprofloxacin proved to be extremely efficient against Plasmodium falciparum and Toxoplasma gondii. Molecular modeling and computational calculations were used to understand the mechanisms of action of these drugs.

Synthesis, Antimicrobial Evaluation, and Docking Studies of Novel 4-Substituted Quinazoline Derivatives as DNA-Gyrase Inhibitors

2010 ◽  
Vol 343 (10) ◽  
pp. 570-576 ◽  
Author(s):  
Shireesha Boyapati ◽  
Umasankar Kulandaivelu ◽  
Srinivas Sangu ◽  
Malla Reddy Vanga
Keyword(s):  
Dna Gyrase ◽  
Docking Studies ◽  
Antimicrobial Evaluation ◽  
Quinazoline Derivatives ◽  
Gyrase Inhibitors

scholarly journals Synthesis, Characterization, Antibacterial Evaluation and Molecular Docking Studies of 2-Azetidinone Derivatives as Novel DNA Gyrase Inhibitors

2015 ◽  
Vol 47 ◽  
pp. 94-108 ◽  
Author(s):  
R. Munavar Sulthana ◽  
S. Darlin Quine
Keyword(s):  
Streptococcus Pyogenes ◽  
Dna Gyrase ◽  
Docking Study ◽  
Spectroscopic Studies ◽  
Docking Studies ◽  
Diffusion Method ◽  
Zone Of Inhibition ◽  
Target Dna ◽  
Gyrase Inhibitors ◽  
Antibacterial Evaluation

Newly designed 2-azetidinone derivatives (4a-e) were synthesized in good yields and characterised by advanced spectroscopic studies. The title compounds were evaluated for qualitative (zone of inhibition) by agar diffusion method against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Streptococcus pyogenes. Some of the analogues were found to have comparable or even more potency than the standard drugs. Docking study was performed to check interaction of synthesized compounds with the target DNA gyrase.

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

Synthesis, antimicrobial activity and molecular modeling study of 3-(5-amino-(2H)-1,2,4-triazol-3-yl]-naphthyridinones as potential DNA-gyrase inhibitors

2018 ◽  
Vol 81 ◽  
pp. 599-611 ◽  
Author(s):  
Noha G. Mohamed ◽  
Mahmoud M. Sheha ◽  
Hoda Y. Hassan ◽  
Lina Jamil M. Abdel-Hafez ◽  
Farghaly A. Omar
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Modeling ◽  
Dna Gyrase ◽  
Molecular Modeling Study ◽  
Gyrase Inhibitors ◽  
Modeling Study

scholarly journals Synthesis, Docking Studies, and In Vitro Evaluation of Some Novel Thienopyridines and Fused Thienopyridine–Quinolines as Antibacterial Agents and DNA Gyrase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3650 ◽  
Author(s):  
Eman M. Mohi El-Deen ◽  
Eman A. Abd El-Meguid ◽  
Sherifa Hasabelnaby ◽  
Eman A. Karam ◽  
Eman S. Nossier
Keyword(s):  
Staphylococcus Aureus ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Inhibition Activity ◽  
Bacterial Strains ◽  
Reference Drug ◽  
E Coli ◽  
Ic50 Values ◽  
Gyrase Inhibitors

A series of novel thienopyridines and pyridothienoquinolines (3a,b–14) was synthesized, starting with 2-thioxo-1,2-dihydropyridine-3-carbonitriles 1a and 1b. All compounds were evaluated for their in vitro antimicrobial activity against six bacterial strains. Compounds 3a,b, 4a, 5b, 6a,b, 7a, 9b, 12b, and 14 showed significant growth inhibition activity against both Gram-positive and Gram-negative bacteria compared with the reference drug. The most active compounds (4a, 7a, 9b, and 12b) against Staphylococcus aureus were also tested for their in vitro inhibitory action on methicillin-resistant Staphylococcus aureus (MRSA). The tested compounds showed promising inhibition activity, with the performance of 12b being equal to gentamicin and that of 7a exceeding it. Moreover, the most promising compounds were also screened for their Escherichia coli DNA gyrase inhibitory activity, compared with novobiocin as a reference DNA gyrase inhibitor. The results revealed that compounds (3a, 3b, 4a, 9b, and 12b) had the highest inhibitory capacity, with IC50 values of 2.26–5.87 µM (that of novobiocin is equal to 4.17 µM). Docking studies were performed to identify the mode of binding of the tested compounds to the active site of E. coli DNA gyrase B.

scholarly journals Design and synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs as Mycobacterium tuberculosis DNA gyrase inhibitors

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Preeti S. Salve ◽  
Prajakta Parchure ◽  
Lisel Araujo ◽  
Rohini S. Kavalapure ◽  
Sunil S. Jalalpure ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Dna Gyrase ◽  
Docking Studies ◽  
Human Populations ◽  
Antitubercular Agents ◽  
Major Health ◽  
Design And Synthesis ◽  
Gyrase Inhibitors

Abstract Background Tuberculosis is evidently a major health threat among human populations worldwide. The current study presents the synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs (4a–o) as potential Mycobacterium tuberculosis DNA gyrase inhibitors. DNA gyrase regulates DNA topology in MTB and has been a target of choice for antibacterial therapy. With this in mind, the synthesized derivatives (4a–o) were subjected to in vitro antitubercular evaluation by the MABA method and were tested for MTB DNA gyrase inhibition by supercoiling assay. Results All the synthesized compounds displayed inhibition of MTB within the MIC range of 1.56–12.5 μM. Further, out of the selected compounds that underwent DNA gyrase inhibition, compound 4o proved to be a potent lead molecule by displaying 82% of enzyme inhibition at 1 μM. All the synthesized derivatives also underwent molecular docking studies to comprehend their hypothetical binding interactions with Mycobacterium smegmatis GyrB. Conclusion All the results suggested that most of the synthesized derivatives inhibited Mycobacterium tuberculosis, and some 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs could act as leads for the development of antitubercular agents.

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