Journal ArticleDOI
Bacterial topoisomerase inhibitors: quinolone and pyridone antibacterial agents.
TLDR
Resume of Structure−Activity Relationships of Quinolones 573 5.11.1.Abstract:
3.1. Chelation 564 3.2. Acid−Base Character 564 3.3. Photochemistry 565 4. In Vitro Antimicrobial Spectra 566 5. Structure−Activity Relationships 568 5.1. N-1 Ethyl Family 568 5.2. N-1 Cyclopropyl Family 568 5.3. N-1 to C-8 Bridged (Tricyclic) Family 568 5.4. N-1 Aryl Family 569 5.5. Positions C-2, C-3, and C-4 570 5.6. C-4a Substituted Analogues 571 5.7. C-5 Substituents 571 5.8. C-6 Substituents 571 5.9. C-7 Substituents 571 5.9.1. Piperazinyl and Related Moieties 572 5.9.2. Pyrrolidinyl and Related Moieties 572 5.9.3. Cyclobutylaminyl and Related Moieties 572 5.9.4. Bicycloaminyl Moieties 572 5.9.5. Carbon-Linked Substituents 572 5.10. Substituents at C-8 573 5.11. Resume of Structure−Activity Relationships of Quinolones 573read more
Citations
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Journal ArticleDOI
Fluorine in pharmaceutical industry: fluorine-containing drugs introduced to the market in the last decade (2001-2011).
Jiang Wang,María Sánchez-Roselló,José Luis Aceña,Carlos del Pozo,Alexander E. Sorochinsky,Alexander E. Sorochinsky,Alexander E. Sorochinsky,Santos Fustero,Vadim A. Soloshonok,Vadim A. Soloshonok,Hong Liu +10 more
TL;DR: Introduced to the Market in the Last Decade (2001−2011) Jiang Wang,† María Sańchez-Rosello,́‡,§ Jose ́ Luis Aceña, Carlos del Pozo,‡ and Hong Liu.
Journal ArticleDOI
Mechanism of quinolone action and resistance.
TL;DR: This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quInolone action against their enzyme targets, and suggests approaches to designing new drugs that display improved activity against resistant strains.
Journal ArticleDOI
Drugging Topoisomerases: Lessons and Challenges
TL;DR: This review discusses how topoisomerase inhibitors kill cells by trapping topoisomersases on DNA rather than by classical enzymatic inhibition, and extends to a novel mechanism of action of PARP inhibitors and could be applied to the targeting of transcription factors.
Journal ArticleDOI
Fluorine in health care: Organofluorine containing blockbuster drugs
TL;DR: The top 10 fluorine containing pharmaceuticals (by US Sales in 2008) are highlighted in this article, where the structures and modes of action of these important drugs compounds are reviewed and representative synthetic routes are highlighted.
Journal ArticleDOI
Type IIA topoisomerase inhibition by a new class of antibacterial agents.
Benjamin D. Bax,Pan F. Chan,Drake S. Eggleston,Drake S. Eggleston,Andrew P. Fosberry,Daniel R. Gentry,Fabrice Gorrec,Fabrice Gorrec,Ilaria Giordano,Michael M. Hann,Alan Joseph Hennessy,Martin Hibbs,Jianzhong Huang,Emma J. Jones,Jo J. Jones,Kristin K. Brown,Ceri J. Lewis,Earl May,Earl May,Martin R. Saunders,Onkar M. P. Singh,Claus Spitzfaden,Carol Shen,Anthony Shillings,Andrew J. Theobald,Alexandre Wohlkonig,Alexandre Wohlkonig,Neil D. Pearson,Michael N. Gwynn +28 more
TL;DR: This work provides new insights into the mechanism of topoisomerase action and a platform for structure-based drug design of a new class of antibacterial agents against a clinically proven, but conformationally flexible, enzyme class.
References
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Stewart T. Cole,Roland Brosch,Julian Parkhill,Thierry Garnier,Carol Churcher,David Harris,Stephen V. Gordon,Karin Eiglmeier,S. Gas,Clifton E. Barry,Fredj Tekaia,K. Badcock,D. Basham,D. Brown,Tracey Chillingworth,R. Connor,Robert L. Davies,K. Devlin,Theresa Feltwell,S. Gentles,N. Hamlin,S. Holroyd,T. Hornsby,Kay Jagels,Anders Krogh,J. McLean,Sharon Moule,Lee Murphy,K. Oliver,J. Osborne,Michael A. Quail,Marie-Adèle Rajandream,Jane Rogers,S. Rutter,K. Seeger,Jason Skelton,Rob Squares,S. Squares,John Sulston,K. Taylor,Sally Whitehead,Bart Barrell +41 more
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DNA topoisomerases: structure, function, and mechanism.
TL;DR: Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the typeIIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes.
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Identification and Structural Characterization of the ATP/ADP-Binding Site in the Hsp90 Molecular Chaperone
Chrisostomos Prodromou,S. Mark Roe,Ronan O'Brien,John E. Ladbury,Peter W. Piper,Laurence H. Pearl +5 more
TL;DR: Crystal structures of complexes between the N-terminal domain of the yeast Hsp90 chaperone and ADP/ATP unambiguously identify a specific adenine nucleotide binding site homologous to the ATP-binding site of DNA gyrase B, suggesting that geldanamycin acts by blocking the binding of nucleotides to Hsp 90 and not the binding to incompletely folded client polypeptides as previously suggested.
Journal ArticleDOI
DNA gyrase: an enzyme that introduces superhelical turns into DNA
TL;DR: Relaxed closed-circular DNA is converted to negatively supercoiled DNA by DNA gyrase by purified from Escherichia coli cells, and the final superhelix density of the DNA can be considerably greater than that found in intracellularly super coiled DNA.
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Type IIA topoisomerase inhibition by a new class of antibacterial agents.
Benjamin D. Bax,Pan F. Chan,Drake S. Eggleston,Drake S. Eggleston,Andrew P. Fosberry,Daniel R. Gentry,Fabrice Gorrec,Fabrice Gorrec,Ilaria Giordano,Michael M. Hann,Alan Joseph Hennessy,Martin Hibbs,Jianzhong Huang,Emma J. Jones,Jo J. Jones,Kristin K. Brown,Ceri J. Lewis,Earl May,Earl May,Martin R. Saunders,Onkar M. P. Singh,Claus Spitzfaden,Carol Shen,Anthony Shillings,Andrew J. Theobald,Alexandre Wohlkonig,Alexandre Wohlkonig,Neil D. Pearson,Michael N. Gwynn +28 more