Synthesis and evaluation of rifabutin analogs against Mycobacterium avium and H37Rv, MDR and NRP Mycobacterium tuberculosis
| Autor: | Mariana Ribeiro, Rogelio Hernández-Pando, M. Céu Costa, David Aguilar, Scott G. Franzblau, Maria Manuela Gaspar, Daniela Fernandes Ramos, Héctor Fabio Bermúdez Orozco, M. Augusta Medeiros, Ricardo Figueiredo, Cristina Moiteiro, M. Cristina S. Lourenço, M. João M. Curto, P. Almeida da Silva, Ivan Neves Junior, Fernanda Sá Spies, M. Eugénia M. Cruz |
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| Rok vydání: | 2009 |
| Předmět: |
Tuberculosis
Rifabutin medicine.drug_class Clinical Biochemistry Antibiotics Antitubercular Agents Pharmaceutical Science Biochemistry Microbiology Mycobacterium tuberculosis Mice Structure-Activity Relationship Drug Resistance Bacterial Drug Discovery medicine Animals Molecular Biology Antibacterial agent Mice Inbred BALB C biology Organic Chemistry biology.organism_classification medicine.disease Multiple drug resistance Molecular Medicine Rifampicin Mycobacterium avium Mycobacterium medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 17:503-511 |
| ISSN: | 0968-0896 |
| Popis: | Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity. RBT analogs 2-11 were synthesized and evaluated against M. avium 1581 and Mycobacterium tuberculosis susceptible and resistant strains in vitro. A selection of candidates were also assayed against non-replicating persistent (NRP) M. tuberculosis. Subsequent in vivo studies with the best preclinical candidate drugs 5 and 8, in a model of progressive pulmonary tuberculosis of Balb/C mice infected either with H(37)Rv drug-sensible strain or with multidrug resistant (MDR) clinical isolates, resistant to all primary antibiotics including rifampicin, were performed. The results disclosed here suggest that 5 and 8 have potential for clinical application. |
| Databáze: | OpenAIRE |
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