Mycobacterium tuberculosis Gyrase Inhibitors as a New Class of Antitubercular Drugs
| Autor: | Alfonso Mendoza, Cindy Richards, Modesto J. Remuiñán, Joaquín Rullas, Iñigo Angulo-Barturen, Delia Blanco, Ermias Woldu, Julia Castro, Esther Pérez-Herrán, Ruben Gonzalez Del Rio, Monica Cacho, María Jesús Vázquez-Muñiz, David Barros, Jose Luis Lavandera, Lluis Ballell, María Cleofé Zapatero-González |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Tuberculosis medicine.drug_class Antitubercular Agents Microbial Sensitivity Tests Topoisomerase-I Inhibitor Pharmacology DNA gyrase Mycobacterium tuberculosis Mice In vivo Drug Discovery medicine Animals Pharmacology (medical) Enzyme Inhibitors Mechanisms of Action: Physiological Effects Mycobacterium bovis biology Drug discovery biology.organism_classification medicine.disease Mice Inbred C57BL Infectious Diseases Female Topoisomerase I Inhibitors Topoisomerase inhibitor Fluoroquinolones |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 59:1868-1875 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.03913-14 |
| Popis: | One way to speed up the TB drug discovery process is to search for antitubercular activity among compound series that already possess some of the key properties needed in anti-infective drug discovery, such as whole-cell activity and oral absorption. Here, we present MGIs, a new series of Mycobacterium tuberculosis gyrase inhibitors, which stem from the long-term efforts GSK has dedicated to the discovery and development of novel bacterial topoisomerase inhibitors (NBTIs). The compounds identified were found to be devoid of fluoroquinolone (FQ) cross-resistance and seem to operate through a mechanism similar to that of the previously described NBTI GSK antibacterial drug candidate. The remarkable in vitro and in vivo antitubercular profiles showed by the hits has prompted us to further advance the MGI project to full lead optimization. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|