Literature DB >> 27595539

The solithromycin journey-It is all in the chemistry.

Prabhavathi Fernandes1, Evan Martens2, Daniel Bertrand3, David Pereira2.   

Abstract

The macrolide class of antibiotics, including the early generation macrolides erythromycin, clarithromycin and azithromycin, have been used broadly for treatment of respiratory tract infections. An increase of treatment failures of early generation macrolides is due to the upturn in bacterial macrolide resistance to 48% in the US and over 80% in Asian countries and has led to the use of alternate therapies, such as fluoroquinolones. The safety of the fluoroquinolones is now in question and alternate antibiotics for the outpatient treatment of community acquired bacterial pneumonia are needed. Telithromycin, approved in 2003, is no longer used owing to serious adverse events, collectively called the 'Ketek effects'. Telithromycin has a side chain pyridine moiety that blocks nicotinic acetylcholine receptors. Blockade of these receptors is known experimentally to cause the side effects seen with telithromycin in patients use. Solithromycin is a new macrolide, the first fluoroketolide, which has been tested successfully in two Phase 3 trials and is undergoing regulatory review at the FDA. Solithromycin is differentiated from telithromycin chemically and biologically in that its side chain is chemically different and does not significantly block nicotinic acetylcholine receptors. Solithromycin was well tolerated and effective in clinical trials. Copyright Â
© 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Entities:  

Keywords:  Antibiotic-resistance; Fluroketolide; Macrolide; Pneumonia; Solithromycin

Mesh:

Substances:

Year:  2016        PMID: 27595539     DOI: 10.1016/j.bmc.2016.08.035

Source DB:  PubMed          Journal:  Bioorg Med Chem        ISSN: 0968-0896            Impact factor:   3.641


  15 in total

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Authors:  George P Dinos
Journal:  Br J Pharmacol       Date:  2017-08-10       Impact factor: 8.739

2.  Fixing the Unfixable: The Art of Optimizing Natural Products for Human Medicine.

Authors:  Audrey E Yñigez-Gutierrez; Brian O Bachmann
Journal:  J Med Chem       Date:  2019-04-26       Impact factor: 7.446

3.  Kinetics of drug-ribosome interactions defines the cidality of macrolide antibiotics.

Authors:  Maxim S Svetlov; Nora Vázquez-Laslop; Alexander S Mankin
Journal:  Proc Natl Acad Sci U S A       Date:  2017-12-11       Impact factor: 11.205

Review 4.  Managing community acquired pneumonia in the elderly - the next generation of pharmacotherapy on the horizon.

Authors:  B Amalakuhan; K L Echevarria; M I Restrepo
Journal:  Expert Opin Pharmacother       Date:  2017-06-21       Impact factor: 3.889

Review 5.  Solithromycin: A Novel Fluoroketolide for the Treatment of Community-Acquired Bacterial Pneumonia.

Authors:  George G Zhanel; Erika Hartel; Heather Adam; Sheryl Zelenitsky; Michael A Zhanel; Alyssa Golden; Frank Schweizer; Bala Gorityala; Philippe R S Lagacé-Wiens; Andrew J Walkty; Alfred S Gin; Daryl J Hoban; Joseph P Lynch; James A Karlowsky
Journal:  Drugs       Date:  2016-12       Impact factor: 9.546

6.  Alternative approaches utilizing click chemistry to develop next-generation analogs of solithromycin.

Authors:  Samer S Daher; Miseon Lee; Xiao Jin; Christiana N Teijaro; Pamela R Barnett; Joel S Freundlich; Rodrigo B Andrade
Journal:  Eur J Med Chem       Date:  2022-02-24       Impact factor: 6.514

7.  Development of Genetically Encoded Biosensors for Reporting the Methyltransferase-Dependent Biosynthesis of Semisynthetic Macrolide Antibiotics.

Authors:  Yiwei Li; Megan Reed; H Tonie Wright; T Ashton Cropp; Gavin J Williams
Journal:  ACS Synth Biol       Date:  2021-09-21       Impact factor: 5.249

8.  In Vitro Activity of the Novel Lactone Ketolide Nafithromycin (WCK 4873) against Contemporary Clinical Bacteria from a Global Surveillance Program.

Authors:  R K Flamm; P R Rhomberg; H S Sader
Journal:  Antimicrob Agents Chemother       Date:  2017-11-22       Impact factor: 5.191

Review 9.  Spotlight on solithromycin in the treatment of community-acquired bacterial pneumonia: design, development, and potential place in therapy.

Authors:  Bryan J Donald; Salim Surani; Harmeet S Deol; Uche J Mbadugha; George Udeani
Journal:  Drug Des Devel Ther       Date:  2017-12-13       Impact factor: 4.162

Review 10.  Nature nurtures the design of new semi-synthetic macrolide antibiotics.

Authors:  Prabhavathi Fernandes; Evan Martens; David Pereira
Journal:  J Antibiot (Tokyo)       Date:  2016-11-30       Impact factor: 2.649

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