In Vitro and In Vivo Activities of Ruthenium(II) Phosphine/Diimine/Picolinate Complexes (SCAR) against Mycobacterium tuberculosis

Autor: Flávia Aparecida Resende, Sergio Roberto de Andrade Leite, Scott G. Franzblau, Eliana Aparecida Varanda, Fernando Rogério Pavan, Alzir A. Batista, Clarice Queico Fujimura Leite, Marília I.F. Barbosa, Mariana Santoro de Camargo, Gustavo Von Poelhsitz, Lucas V. P. da Cunha, Sang H. Cho
Přispěvatelé: Universidade Estadual Paulista (Unesp), Universidade Federal de Uberlândia (UFU), Univ Federal de São Carlos, University of Illinois at Chicago
Rok vydání: 2013
Předmět:
Bacterial Diseases
kanamycin
antibiotic resistance
Mouse
Applied Microbiology
Antitubercular Agents
ethambutol
lcsh:Medicine
acute toxicity
Pharmacology
rifampicin
growth inhibition
ruthenium complex
Mice
antibacterial activity
Coordination Complexes
lcsh:Science
Picolinic Acids
media_common
Multidisciplinary
biology
Chemistry
drug cytotoxicity
drug effect
Isoniazid
Animal Models
Ames test
female
Infectious Diseases
Medicine
Female
Imines
imine
moxifloxacin
Research Article
medicine.drug
Drug
isoniazid
Drugs and Devices
in vitro study
Drug Research and Development
Tuberculosis
streptomycin
Phosphines
media_common.quotation_subject
animal experiment
Microbial Sensitivity Tests
minimum inhibitory concentration
Microbiology
Ruthenium
animal tissue
in vivo study
Mycobacterium tuberculosis
picolinic acid
Model Organisms
In vivo
Drug Resistance
Bacterial
Toxicity Tests
Acute
medicine
Animals
Humans
controlled study
Biology
mouse
Ethambutol
nonhuman
Mutagenicity Tests
LD 50
lcsh:R
mutagenicity
Extensively drug-resistant tuberculosis
phosphine
medicine.disease
biology.organism_classification
Mice
Inbred C57BL
drug structure
Pharmacodynamics
concentration response
Mutagenesis
lcsh:Q
Medicinal Chemistry
Rifampicin
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 5, p e64242 (2013)
Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0064242
Popis: Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:29:32Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:48:30Z : No. of bitstreams: 1 2-s2.0-84878384875.pdf: 323671 bytes, checksum: 87018b1bd2432bd7aabb7476208d8cf7 (MD5) Made available in DSpace on 2014-05-27T11:29:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-05-28 Rifampicin, discovered more than 50 years ago, represents the last novel class of antibiotics introduced for the first-line treatment of tuberculosis. Drugs in this class form part of a 6-month regimen that is ineffective against MDR and XDR TB, and incompatible with many antiretroviral drugs. Investments in R&D strategies have increased substantially in the last decades. However, the number of new drugs approved by drug regulatory agencies worldwide does not increase correspondingly. Ruthenium complexes (SCAR) have been tested in our laboratory and showed promising activity against Mycobacterium tuberculosis. These complexes showed up to 150 times higher activity against MTB than its organic molecule without the metal (free ligand), with low cytotoxicity and high selectivity. In this study, promising results inspired us to seek a better understanding of the biological activity of these complexes. The in vitro biological results obtained with the SCAR compounds were extremely promising, comparable to or better than those for first-line drugs and drugs in development. Moreover, SCAR 1 and 4, which presented low acute toxicity, were assessed by Ames test, and results demonstrated absence of mutagenicity. © 2013 Pavan et al. Department of Biological Sciences College of Pharmacy Univ Estadual Paulista, Araraquara, São Paulo Chemistry Institute Univ Federal de Uberlândia, Uberlândia, Minas Gerais Department of Chemistry Univ Federal de São Carlos, São Carlos, São Paulo Chemistry Institute Univ Estadual Paulista, Araraquara, São Paulo Institute for Tuberculosis Research College of Pharmacy University of Illinois at Chicago, Chicago Department of Biological Sciences College of Pharmacy Univ Estadual Paulista, Araraquara, São Paulo Chemistry Institute Univ Estadual Paulista, Araraquara, São Paulo
Databáze: OpenAIRE
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