5,222 results match your criteria dna gyrase


Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents.

Sci Rep 2021 Apr 12;11(1):7846. Epub 2021 Apr 12.

Chemistry Department, Faculty of Science, Jazan University, Jazan, Saudi Arabia.

A novel series of substituted 4,6-dimethyl-2-oxo-1-(thiazol-2-ylamino)-1,2-dihydropyridine-3-carbonitrile derivatives 6, 9, 13, 15, and 17 was synthesized in a good to excellent yield from the reaction of 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)thiourea with 2-oxo-N'-arylpropanehydrazonoyl chloride, chloroacetone, α-bromoketones, ethyl chloroacetate, and 2,3-dichloroquinoxaline, respectively. The potential DNA gyrase inhibitory activity was examined using in silico molecular docking simulation. The novel thiazoles exhibit dock score values between - 6. Read More

View Article and Full-Text PDF

GyrA Tower Domain Interacts with QnrB1 Loop B and Plays an Important Role in QnrB1 Protection from Quinolone Inhibition.

Antimicrob Agents Chemother 2021 Apr 12. Epub 2021 Apr 12.

Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA;

The Qnr pentapeptide repeat proteins interact with DNA gyrase and protect it from quinolone inhibition. The two external loops, particularly the larger loop B, of Qnr proteins are essential for quinolone protection of DNA gyrase. The specific QnrB1 interaction sites on DNA gyrase are not known. Read More

View Article and Full-Text PDF

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

Bioorg Chem 2021 Apr 1;111:104885. Epub 2021 Apr 1.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, 82524 Sohag, Egypt. Electronic address:

New antibacterial drugs are urgently needed to tackle the rapid rise in multi-drug resistant bacteria. DNA gyrase is a validated target for the development of new antibacterial drugs. Thus, in the present investigation, a novel series of 1,2,4-oxadiazole-chalcone/oxime (6a-f) and (7a-f) were synthesized and characterized by IR, NMR (H and C) and elemental analyses. Read More

View Article and Full-Text PDF

The pentapeptide-repeat protein, MfpA, interacts with mycobacterial DNA gyrase as a DNA T-segment mimic.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Department of Biological Chemistry, John Innes Centre, NR4 7UH Norwich, United Kingdom;

DNA gyrase, a type II topoisomerase, introduces negative supercoils into DNA using ATP hydrolysis. The highly effective gyrase-targeted drugs, fluoroquinolones (FQs), interrupt gyrase by stabilizing a DNA-cleavage complex, a transient intermediate in the supercoiling cycle, leading to double-stranded DNA breaks. MfpA, a pentapeptide-repeat protein in mycobacteria, protects gyrase from FQs, but its molecular mechanism remains unknown. Read More

View Article and Full-Text PDF

Effectiveness of Fluoroquinolones with Difluoropyridine Derivatives as R1 Groups on the DNA Gyrase in the Presence and Absence of Plasmid-Encoded Quinolone Resistance Protein QnrB19.

Microb Drug Resist 2021 Apr 9. Epub 2021 Apr 9.

Division of Bioresources, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.

WQ-3810 has strong inhibitory activity against and other fluoroquinolone-resistant pathogens. The unique potentiality of this is attributed to 6-amino-3,5-difluoropyridine-2-yl at R1 group. The aim of this study was to examine WQ-3810 and its derivatives WQ-3334 and WQ-4065 as the new drug candidate for wild-type and that carrying QnrB19. Read More

View Article and Full-Text PDF

Overexpression of A Gene Increases Ciprofloxacin Resistance in .

Int J Microbiol 2021 22;2021:6689186. Epub 2021 Mar 22.

Grupo de Investigación en Microbiología, Industria y Ambiente (GIMIA), Facultad de Ciencias Básicas, Universidad Santiago de Cali, Cali, Colombia.

Fluoroquinolones (FQs) are antibiotics useful in the treatment of drug-resistant tuberculosis, but FQ-resistant mutants can be selected rapidly. Although mutations in the DNA gyrase are the principal cause of this resistance, pentapeptide proteins have been found to confer low-level FQ resistance in Gram-negative bacteria. MfpA is a pentapeptide repeat protein conserved in mycobacterial chromosomes, where it is adjacent to a group of four highly conserved genes termed a . Read More

View Article and Full-Text PDF

Comparative Study on the Essential Oils from Five Wild Egyptian Species: Effective Extraction Techniques, Antimicrobial Activity and In-Silico Analyses.

Antibiotics (Basel) 2021 Mar 3;10(3). Epub 2021 Mar 3.

Chemistry of Medicinal Plants Department, National Research Centre, 33 El-Bohouth St., Dokki, Giza 12622, Egypt.

The genus is recognized in folk medicine for anti-inflammatory, anti-itch, antitussive, purgative, astringent, and tonic activities. To study the chemical determinant for antimicrobial activity essential oils (EOs), five species were analyzed including: , , , and . Conventional hydro-distillation (HD) and microwave-assisted extraction (MAE), as new green technologies, were compared for the extraction of essential oils. Read More

View Article and Full-Text PDF

A New Family of Benzo[]Chromene Based Azo Dye: Synthesis, In-Silico and DFT Studies with In Vitro Antimicrobial and Antiproliferative Assessment.

Int J Mol Sci 2021 Mar 10;22(6). Epub 2021 Mar 10.

Department of Chemistry, College of Sciences, Taibah University, Yanbu 30799, Saudi Arabia.

The high biological activity of the chromene compounds coupled with the intriguing optical features of azo chromophores prompted our desire to construct novel derivatives of chromene incorporating azo moieties 4a-l, which have been prepared via a three-component reaction of 1-naphthalenol-4-[(4-ethoxyphenyl) azo], 1, with the benzaldehyde derivatives and malononitrile. The structural identities of the azo-chromene 4a-l were confirmed on the basis of their spectral data and elemental analysis, and a UV-visible study was performed in a Dimethylformamide (DMF) solution for these molecules. Additionally, the antimicrobial activity was investigated against four human pathogens (Gram-positive and Gram-negative bacteria) and four fungi, employing an agar well diffusion method, with their minimum inhibitory concentrations being reported. Read More

View Article and Full-Text PDF

Allicin, the Odor of Freshly Crushed Garlic: A Review of Recent Progress in Understanding Allicin's Effects on Cells.

Molecules 2021 Mar 10;26(6). Epub 2021 Mar 10.

Department of Plant Physiology, RWTH Aachen University, 52056 Aachen, Germany.

The volatile organic sulfur compound allicin (diallyl thiosulfinate) is produced as a defense substance when garlic () tissues are damaged, for example by the activities of pathogens or pests. Allicin gives crushed garlic its characteristic odor, is membrane permeable and readily taken up by exposed cells. It is a reactive thiol-trapping sulfur compound that -thioallylates accessible cysteine residues in proteins and low molecular weight thiols including the cellular redox buffer glutathione (GSH) in eukaryotes and Gram-negative bacteria, as well as bacillithiol (BSH) in Gram-positive firmicutes. Read More

View Article and Full-Text PDF

Synthesis of Computationally Designed 2,5(6)-Benzimidazole Derivatives via Pd-Catalyzed Reactions for Potential DNA Gyrase B Inhibition.

Molecules 2021 Mar 2;26(5). Epub 2021 Mar 2.

Coimbra Chemistry Centre, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal.

A pharmacophore model for inhibitors of 's DNA Gyrase B was developed, using computer-aided drug design. Subsequently, docking studies showed that 2,5(6)-substituted benzimidazole derivatives are promising molecules, as they possess key hydrogen bond donor/acceptor groups for an efficient interaction with this bacterial target. Furthermore, 5(6)-bromo-2-(2-nitrophenyl)-1-benzimidazole, selected as a core molecule, was prepared on a multi-gram scale through condensation of 4-bromo-1,2-diaminobenzene with 2-nitrobenzaldehyde using a sustainable approach. Read More

View Article and Full-Text PDF

N-1, 3-Benzenedicarbonyl-Bis-(Amino Acid) and Dipeptide Candidates: Synthesis, Cytotoxic, Antimicrobial and Molecular Docking Investigation.

Drug Des Devel Ther 2021 25;15:1315-1332. Epub 2021 Mar 25.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.

Purpose: The objective of our work was to prepare a potent and safe antimicrobial and anticancer agents, through synthesis of several peptides and examine their biological activities, namely as, cytotoxically potent and antimicrobial and antifungal agents.

Introduction: Multidrug-resistant microbial strains have arisen against all antibiotics in clinical use. Infections caused by these bacteria threaten global public health and are associated with high mortality rates. Read More

View Article and Full-Text PDF

Repurposing celecoxib analogues as leads for antibiotics.

Future Med Chem 2021 Mar 30. Epub 2021 Mar 30.

School of Pharmacy, Jiangsu Food & Pharmaceutical Science College, Huai'an, Jiangsu 223003, China.

There is an urgent need for new antibiotics and alternative strategies to combat bacterial pathogens. Molecular docking, antibacterial evaluation and , cytotoxicity assessment and enzyme inhibition analyses were performed. Compound exhibited antimicrobial activity against (MIC: 4 μg/ml), various clinically isolated strains of MRSA (MIC: 4-16 μg/ml) and (MIC: 4 μg/ml) when combined with subinhibitory concentrations of colistin B. Read More

View Article and Full-Text PDF

Analyzing possible native functions of the quinolone resistance gene in .

Antimicrob Agents Chemother 2021 Mar 29. Epub 2021 Mar 29.

Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

The worldwide distribution of genes found on plasmids and their presence on the chromosomes of aquatic bacteria, like , one of the suspected sources, suggests an origin before the development of synthetic quinolones. However, their native function remains unknown. Previous work indicated that expression of in was induced by cold shock. Read More

View Article and Full-Text PDF

Acetylenic Replacement of Albicidin's Methacrylamide Residue Circumvents Detrimental (E)-(Z)-Photoisomerization and Preserves Antibacterial Activity.

Chemistry 2021 Mar 26. Epub 2021 Mar 26.

Technische Universität Berlin: Technische Universitat Berlin, Chemistry, Straße des 17. Juni 124, Sekr. TC 2, 10623, Berlin, GERMANY.

The natural product albicidin is a highly potent inhibitor of bacterial DNA gyrase. Its outstanding activity, particularly against Gram-negative pathogens, qualifies it as a promising lead structure in the search for new antibacterial drugs. However, here we show that the N-terminal cinnamoyl moiety of albicidin is susceptible to photochemical ( E )-( Z )-isomerization. Read More

View Article and Full-Text PDF

Two antibacterial spiro compounds from the roots of wall: evidence from molecular docking.

Nat Prod Res 2021 Mar 22:1-8. Epub 2021 Mar 22.

R&D Centre in Pharmaceutical Sciences and Applied Chemistry, Poona College of Pharmacy Campus, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India.

Bioassay-guided isolation from acetone extract of the roots of Wall yielded two spiro compounds ( and ). The structures of these compounds were determined on the basis of spectroscopic techniques such as IR, MS, 1 D and 2 D- NMR. The acetone extract, fractions and the isolated two compounds were investigated for their antibacterial activity against two gram negative (, ) and two gram positive (, ) bacterial strains. Read More

View Article and Full-Text PDF

TEX264 at the intersection of autophagy and DNA repair.

Autophagy 2021 Mar 17:1-10. Epub 2021 Mar 17.

Medical Research Council (MRC) Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, UK.

TEX264 (testes expressed gene 264) is a single-pass transmembrane protein, consisting of an N-terminal hydrophobic region, a gyrase inhibitory (GyrI)-like domain, and a loosely structured C terminus. TEX264 was first identified as an endoplasmic reticulum (ER)-resident Atg8-family-binding protein that mediates the degradation of portions of the ER during starvation (i.e. Read More

View Article and Full-Text PDF

Membrane active 7-thiazoxime quinolones as novel DNA binding agents to decrease the genes expression and exert potent anti-methicillin-resistant Staphylococcus aureus activity.

Eur J Med Chem 2021 Mar 10;217:113340. Epub 2021 Mar 10.

Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China. Electronic address:

A novel class of 7-thiazoxime quinolones was developed as potential antimicrobial agents for the sake of bypassing resistance of quinolones. Biological assays revealed that some constructed 7-thiazoxime quinolones possessed effective antibacterial efficiency. Methyl acetate oxime derivative 6l exhibited 32-fold more active than ciprofloxacin against MRSA, which also possessed rapidly bactericidal ability and low toxicity towards mammalian cells. Read More

View Article and Full-Text PDF

Towards Conformation-Sensitive Inhibition of Gyrase: Implications of Mechanistic Insight for the Identification and Improvement of Inhibitors.

Molecules 2021 Feb 25;26(5). Epub 2021 Feb 25.

Biophysical Chemistry, Institute for Physical Chemistry, University of Münster, 48149 Münster, Germany.

Gyrase is a bacterial type IIA topoisomerase that catalyzes negative supercoiling of DNA. The enzyme is essential in bacteria and is a validated drug target in the treatment of bacterial infections. Inhibition of gyrase activity is achieved by competitive inhibitors that interfere with ATP- or DNA-binding, or by gyrase poisons that stabilize cleavage complexes of gyrase covalently bound to the DNA, leading to double-strand breaks and cell death. Read More

View Article and Full-Text PDF
February 2021

Bioactive Alkaloids from Genus : Mechanistic Interpretation of Their Antimicrobial and Potential SARS-CoV-2 Inhibitory Activity Using Molecular Modelling.

Int J Mol Sci 2021 Feb 13;22(4). Epub 2021 Feb 13.

Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.

Genus represents a widely spread genus of fungi that is highly popular for possessing potent medicinal potential comprising mainly antimicrobial, cytotoxic and antioxidant properties. They are highly attributed to its richness by alkaloids, terpenes, steroids and polyketons. This review aimed to comprehensively explore the diverse alkaloids isolated and identified from different species of genus that were found to be associated with different marine organisms regarding their chemistry and biology. Read More

View Article and Full-Text PDF
February 2021

Exonuclease VII repairs quinolone-induced damage by resolving DNA gyrase cleavage complexes.

Sci Adv 2021 Mar 3;7(10). Epub 2021 Mar 3.

Laboratory of Molecular Pharmacology, Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

The widely used quinolone antibiotics act by trapping prokaryotic type IIA topoisomerases, resulting in irreversible topoisomerase cleavage complexes (TOPcc). Whereas the excision repair pathways of TOPcc in eukaryotes have been extensively studied, it is not known whether equivalent repair pathways for prokaryotic TOPcc exist. By combining genetic, biochemical, and molecular biology approaches, we demonstrate that exonuclease VII (ExoVII) excises quinolone-induced trapped DNA gyrase, an essential prokaryotic type IIA topoisomerase. Read More

View Article and Full-Text PDF

Topological stress is responsible for the detrimental outcomes of head-on replication-transcription conflicts.

Cell Rep 2021 Mar;34(9):108797

Department of Biochemistry, Light Hall, Vanderbilt University, Nashville, TN, USA. Electronic address:

Conflicts between the replication and transcription machineries have profound effects on chromosome duplication, genome organization, and evolution across species. Head-on conflicts (lagging-strand genes) are significantly more detrimental than codirectional conflicts (leading-strand genes). The fundamental reason for this difference is unknown. Read More

View Article and Full-Text PDF

Design, synthesis, antibacterial evaluation, and computational studies of hybrid oxothiazolidin-1,2,4-triazole scaffolds.

Arch Pharm (Weinheim) 2021 Mar 3:e2000473. Epub 2021 Mar 3.

Bioorganic and Medicinal Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology & Sciences, Prayagraj, Uttar Pradesh, India.

Bacterial infections are a serious threat to human health due to the development of resistance against the presently used antibiotics. The problem of growing and widespread antibiotic resistance is only getting worse with the shortage of new classes of antibiotics, creating a substantial unmet medical need in the treatment of serious bacterial infections. Therefore, in the present work, we report 18 novel hybrid thiazolidine-1,2,4-triazole derivatives as DNA gyrase inhibitors. Read More

View Article and Full-Text PDF

Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives.

Chem Biol Drug Des 2021 Feb 26. Epub 2021 Feb 26.

School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, WA, Australia.

Several rationally designed isoniazid (INH), pyrazinamide (PZA) and ciprofloxacin (CPF) derivatives were conveniently synthesized and evaluated in vitro against H37Rv Mycobacterium tuberculosis (M. tb) strain. CPF derivative 16 displayed a modest activity (MIC = 16 µg/ml) and was docked into the M. Read More

View Article and Full-Text PDF
February 2021

Facilitating Compound Entry as a Means to Discover Antibiotics for Gram-Negative Bacteria.

Acc Chem Res 2021 Mar 26;54(6):1322-1333. Epub 2021 Feb 26.

Department of Chemistry Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Urbana, Illinois 61801, United States.

ConspectusIt has been over half a century since the last class of antibiotics active against the most problematic Gram-negative bacteria was approved by the Food and Drug Administration (FDA). The major challenge with developing antibiotics to treat these infections is not drug-target engagement but rather the inability of most small molecules to traverse the Gram-negative membranes, be retained, and accumulate within the cell. Despite an abundance of lead compounds, limited understanding of the physicochemical properties needed for compound accumulation (or avoidance of efflux) in Gram-negative bacteria has precluded a generalizable approach for developing Gram-negative antibiotics. Read More

View Article and Full-Text PDF

Changes in the topology of DNA replication intermediates: Important discrepancies between in vitro and in vivo.

Bioessays 2021 Feb 25:e2000309. Epub 2021 Feb 25.

Directorate of Research and Postgraduate Studies, Polytechnic School, National University of Asunción, P, San Lorenzo, Paraguay.

The topology of DNA duplexes changes during replication and also after deproteinization in vitro. Here we describe these changes and then discuss for the first time how the distribution of superhelical stress affects the DNA topology of replication intermediates, taking into account the progression of replication forks. The high processivity of Topo IV to relax the left-handed (+) supercoiling that transiently accumulates ahead of the forks is not essential, since DNA gyrase and swiveling of the forks cooperate with Topo IV to accomplish this task in vivo. Read More

View Article and Full-Text PDF
February 2021

Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents.

Bioorg Chem 2021 Apr 3;109:104692. Epub 2021 Feb 3.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, PR China; Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, United Kingdom. Electronic address:

A series of ursolic acid (UA), oleanolic acid (OA) and 18β-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus spp. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. Read More

View Article and Full-Text PDF

Antibacterial mechanisms of Aronia melanocarpa (Michx.), Chaenomeles superba Lindl. and Cornus mas L. leaf extracts.

Food Chem 2021 Jul 6;350:129218. Epub 2021 Feb 6.

Institute of Food Technology and Analysis, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland. Electronic address:

The aim of this study was to investigate the in vitro antibacterial mechanisms of Aronia melanocarpa, Chaenomeles superba, and Cornus mas leaf extracts towards meat spoilage and pathogenic bacteria. The extracts decreased bacterial viability after 24 h and 48 h of incubation. Acting as prooxidants, the extracts induced intracellular ROS (reactive oxygen species) generation in bacteria cells, with C. Read More

View Article and Full-Text PDF

Nybomycin inhibits both types of DNA gyrase - fluoroquinolone-sensitive and fluoroquinolone-resistant.

Antimicrob Agents Chemother 2021 Feb 16. Epub 2021 Feb 16.

Department of Chemistry, Faculty of Bioengineering and Bioinformatics and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia.

Bacterial type II topoisomerases, DNA gyrase and topoisomerase IV, are targets of many antibiotics including fluoroquinolones (FQs). Unfortunately, a number of bacterial species easily acquire resistance to FQs by mutations in either DNA gyrase or topoisomerase IV genes. The emergence of resistant pathogenic strains is a global problem in healthcare, therefore, identifying alternative pathways to thwart their persistence is the current frontier in drug discovery. Read More

View Article and Full-Text PDF
February 2021

In silico Molecular Docking, DFT Analysis and ADMET Studies of Carbazole Alkaloid and Coumarins from Roots of : A Potent Inhibitor for Quorum Sensing.

Adv Appl Bioinform Chem 2021 5;14:13-24. Epub 2021 Feb 5.

Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, Adama, 1888, Ethiopia.

Introduction: In modern drug design, in silico methods are largely used to understand drug-receptor interactions and quantum chemical properties. In the present study, a computational de novo design approach was used to confirm mode of binding for antibacterial activity, elucidating quantum chemical properties and ADMET-drug-likeness of carbazole alkaloid () and three coumarins (-) isolated from roots of .

Methods: Docking studies were performed with DNA-Gyrase (6F86) and LasR binding domain (2UV0) employing a flexible ligand docking approach using AutoDock Vina. Read More

View Article and Full-Text PDF
February 2021

Replication and partitioning of the apicoplast genome of Toxoplasma gondii is linked to the cell cycle and requires DNA polymerase and gyrase.

Int J Parasitol 2021 Feb 11. Epub 2021 Feb 11.

Department of Cellular Biology, University of Georgia, Athens, GA, USA; Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA. USA.

Apicomplexans are the causative agents of numerous important infectious diseases including malaria and toxoplasmosis. Most of them harbour a chloroplast-like organelle called the apicoplast that is essential for the parasites' metabolism and survival. While most apicoplast proteins are nuclear encoded, the organelle also maintains its own genome, a 35 kb circle. Read More

View Article and Full-Text PDF
February 2021