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2020-12-26
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SYNTHESIS AND EVALUATION OF RIFABUTIN ANALOGS AGAINST MYCOBACTEIUM AVIUM AND H(37) RV, MDR AND NRP MYCOBACTERIUM TUBERCULOSIS
Figueiredo, Ricardo et al. | Date Issued: 2009
Author
Figueiredo, Ricardo
Moiteiro, Cristina
Medeiros, M. Augusta
Silva, P. Almeida da
Ramos, D.
Spies, F.
Ribeiro, M. O.
Lourenço, M. Cristina S.
Neves Júnior, I. N.
Gaspar, M. Manoela
Cruz, M. Eugénia M.
Curto, M. João Marcelo
Franzblau, S. G.
Orozco, H.
Aguilar, D.
Hernandez-Pando, R.
Costa, M. Céu
Affilliation
Instituto Nacional de Engenharia, Tecnologia e Inovação. Lisboa, Portugal.
Instituto Nacional de Engenharia, Tecnologia e Inovação. Lisboa, Portugal.
Instituto Nacional de Engenharia, Tecnologia e Inovação. Lisboa, Portugal.
Universidade Federal do Rio Grande. Rio Grande, RS, Brasil.
Universidade Federal do Rio Grande. Rio Grande, RS, Brasil.
Universidade Federal do Rio Grande. Rio Grande, RS, Brasil.
Universidade Federal do Rio Grande. Rio Grande, RS, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Engenharia, Tecnologia e Inovação. Lisboa, Portugal.
Instituto Nacional de Engenharia, Tecnologia e Inovação. Lisboa, Portugal.
Instituto Nacional de Engenharia, Tecnologia e Inovação. Lisboa, Portugal.
.University of Illinois. Institute for Tuberculosis Research. Chicago, IL, USA.
National Institute of Medical Sciences and Nutrition Salvador Zubirán. Mexico, DF, Mexico
National Institute of Medical Sciences and Nutrition Salvador Zubirán. Mexico, DF, Mexico
National Institute of Medical Sciences and Nutrition Salvador Zubirán. Mexico, DF, Mexico.
Instituto Nacional de Engenharia, Tecnologia e Inovação. Lisboa, Portugal.
Abstract
Clinical utility of rifabutin1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) aswell 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 H37Rv drug–sensible strain or with multidrug resistant (MDR) clinical isolates, resistant toall primary antibiotics including rifampicin, were performed. The results disclosed here suggest that 5 and 8 have potential for clinical application.
Keywords
Tuberculosis
Mycobacterium avium
Mycobacterium tuberculosis
Anti-tuberculosis drugs
 
Publisher
Elsevier
Citation
FIGUEIREDO, Ricardo et al. Synthesis and evaluation of rifabutin analogs against Mycobacterium avium and H37Rv, MDR and NRPMycobacterium tuberculosis. Bioorganic and Medicinal Chemistry, v. 17, p. 503-511, 2009.
DOI
10.1016/j.bmc.2008.12.006
ISSN
0968-0896