scholarly journals Lead Identification of 8-(Methylamino)-2-oxo-1,2-dihydroquinoline Derivatives as DNA Gyrase Inhibitors: Hit-to-Lead Generation Involving Thermodynamic Evaluation

ACS Omega ◽  
2020 ◽  
Vol 5 (17) ◽  
pp. 10145-10159 ◽  
Author(s):  
Fumihito Ushiyama ◽  
Hideaki Amada ◽  
Tomoki Takeuchi ◽  
Nozomi Tanaka-Yamamoto ◽  
Harumi Kanazawa ◽  
...  
Keyword(s):  
Dna Gyrase ◽  
Thermodynamic Evaluation ◽  
Lead Identification ◽  
Lead Generation ◽  
Gyrase Inhibitors

scholarly journals Assays, Surrogates, and Alternative Technologies for a TB Lead Identification Program Targeting DNA Gyrase ATPase

2014 ◽  
Vol 20 (2) ◽  
pp. 265-274 ◽  
Author(s):  
Vaishali Humnabadkar ◽  
Prashanti Madhavapeddi ◽  
Halesha Basavarajappa ◽  
Md. Gulebahar Sheikh ◽  
Rajendra Rane ◽  
...  
Keyword(s):  
Mycobacterium Smegmatis ◽  
Specific Activity ◽  
Dna Gyrase ◽  
Enzyme Concentration ◽  
Alternative Technologies ◽  
Lead Identification ◽  
Drug Discovery Program ◽  
Lead Generation ◽  
Nanomolar Range

Mycobacterium tuberculosis (Mtb) DNA gyrase ATPase was the target of a tuberculosis drug discovery program. The low specific activity of the Mtb ATPase prompted the use of Mycobacterium smegmatis (Msm) enzyme as a surrogate for lead generation, since it had 20-fold higher activity. Addition of GyrA or DNA did not significantly increase the activity of the Msm GyrB ATPase, and an assay was developed using GyrB alone. Inhibition of the Msm ATPase correlated well with inhibition of Mtb DNA gyrase supercoiling across three chemical scaffolds, justifying its use. As the IC50 of compounds approached the enzyme concentration, surrogate assays were used to estimate potencies (e.g., the shift in thermal melt of Mtb GyrB, which correlated well with IC50s >10 nM). Analysis using the Morrison equation enabled determination of [Formula: see text]s in the sub-nanomolar range. Surface plasmon resonance was used to confirm these IC50s and measure the Kds of binding, but a fragment of Mtb GyrB had to be used. Across three scaffolds, the dissociation half life, t1/2, of the inhibitor-target complex was ≤8 min. This toolkit of assays was developed to track the potency of enzyme inhibition and guide the chemistry for progression of compounds in a lead identification program.

New 1,4-dihydro[1,8]naphthyridine derivatives as DNA gyrase inhibitors

2017 ◽  
Vol 27 (5) ◽  
pp. 1162-1168 ◽  
Author(s):  
Hülya Karaca Gençer ◽  
Serkan Levent ◽  
Ulviye Acar Çevik ◽  
Yusuf Özkay ◽  
Sinem Ilgın
Keyword(s):  
Dna Gyrase ◽  
Gyrase Inhibitors

Synthesis and antibacterial activity of a novel series of DNA gyrase inhibitors: 5-[(E)-2-arylvinyl]pyrazoles

2005 ◽  
Vol 15 (19) ◽  
pp. 4299-4303 ◽  
Author(s):  
Akihiko Tanitame ◽  
Yoshihiro Oyamada ◽  
Keiko Ofuji ◽  
Hideo Terauchi ◽  
Motoji Kawasaki ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Dna Gyrase ◽  
Gyrase Inhibitors

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

ChemInform Abstract: A Concise, Practical Synthesis of the Pyrido(3.2.1-ij)cinnoline Ring System of Potent DNA Gyrase Inhibitors.

ChemInform ◽  
2010 ◽  
Vol 26 (46) ◽  
pp. no-no
Author(s):  
D. BARRETT ◽  
H. SASAKI ◽  
H. TSUTSUMI ◽  
M. MURATA ◽  
T. TERASAWA ◽  
...  
Keyword(s):  
Dna Gyrase ◽  
Ring System ◽  
Practical Synthesis ◽  
Gyrase Inhibitors

scholarly journals Synthesis, Characterization and in vitro Antimicrobial Evaluation of Chalconeimine Derivatives as Potential Inhibitors against Enzymes Produced from S. aureus: A Computational Approach

2019 ◽  
Vol 31 (10) ◽  
pp. 2157-2164
Author(s):  
B. Prithivirajan ◽  
M. Jebastin Sonia Jas ◽  
G. Marimuthu
Keyword(s):  
Antibacterial Agents ◽  
Dna Gyrase ◽  
Bacterial Strains ◽  
Bacterial Proteins ◽  
Antibiotic Drug ◽  
In Vitro Antibacterial Activity ◽  
Antimicrobial Evaluation ◽  
Potential Inhibitors ◽  
Gyrase Inhibitors

(Z)-1-(Benzo[d][1,3]dioxol-5-yl)-3-(4-(difluoromethoxy)-3-hydroxyphenyl)prop-2-en-1-one hydrazone derivatives pronounced in this manuscript represents a new collection of antibacterial agents in addition to the DNA gyrase inhibitors. Efforts had been made to synthesize those chalcone-hydrazone derivatives (4a-e) in good yields. The literature survey confirms that nano-ZnO as heterogeneous catalyst has obtained big interest because of its ecofriendly nature and has been explored as a effective catalyst for several organic ameliorations. Subsequently, induced by way of these observations and in continuation to our interest in organic synthesis with using nanocatalyst. in vitro Antibacterial activity has been evaluated towards Gram-positive and Gram-negative bacterial strains for all compounds. So one can discover the affinity to bacterial proteins docking have a look at have been carried out for 5 synthesized derivatives, antibiotic drug and co-crystallized ligands with special mechanism of action DNA gyrase B and methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) the usage of AutoDock 4.

scholarly journals Synthesis, Structure and Antibacterial Activity of Potent DNA Gyrase Inhibitors: N′-Benzoyl-3-(4-Bromophenyl)-1H-Pyrazole-5-Carbohydrazide Derivatives

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e69751 ◽  
Author(s):  
Juan Sun ◽  
Peng-Cheng Lv ◽  
Yong Yin ◽  
Rong-Ju Yuan ◽  
Jian Ma ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Dna Gyrase ◽  
Gyrase Inhibitors
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