Discovery and in vivo evaluation of alcohol-containing benzothiazoles as potent dual-targeting bacterial DNA supercoiling inhibitors
| Autor: | Alastair Logan, James T Palmer, B. Narasinga Rao, Neil R. Stokes, Ian Collins, Tarun Shukla, James M. Bennett, Anil K Srivastava, Paul Lancett, Leigh Ford, Pitt Gary Robert William, Helena Thomaides-Brears, Lorraine C. Axford, Stephanie Barker, Anju Yadav, Amit Kumar Singh, David T. Davies, Michael Blair, Craig J. Morton, David J. Haydon, Carlie T. Gannon, Daniel A. Offermann, Christopher J. Lunniss |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
DNA
Bacterial Staphylococcus Carboxylic acid Clinical Biochemistry Pharmaceutical Science Microbial Sensitivity Tests Biochemistry DNA gyrase Structure-Activity Relationship In vivo Drug Discovery Structure–activity relationship Benzothiazoles Molecular Biology chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure biology DNA Superhelical Drug discovery Topoisomerase Organic Chemistry Haemophilus influenzae Anti-Bacterial Agents chemistry Alcohols biology.protein Molecular Medicine DNA supercoil Antibacterial activity |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 24:4215-4222 |
| ISSN: | 0960-894X |
| Popis: | A series of dual-targeting, alcohol-containing benzothiazoles has been identified with superior antibacterial activity and drug-like properties. Early lead benzothiazoles containing carboxylic acid moieties showed efficacy in a well-established in vivo model, but inferior drug-like properties demanded modifications of functionality capable of demonstrating superior efficacy. Eliminating the acid group in favor of hydrophilic alcohol moieties at C5, as well as incorporating solubilizing groups at the C7 position of the core ring provided potent, broad-spectrum Gram-positive antibacterial activity, lower protein binding, and markedly improved efficacy in vivo. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect