title: In vitro and in vivo activities of ruthenium(II) phosphine/diimine/picolinate complexes (SCAR) against Mycobacterium tuberculosis.
abstract: 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.
authors.affiliation: Department of Biological Sciences, College of Pharmacy, Univ Estadual Paulista, Araraquara, São Paulo, Brazil. fernandopavan@fcfar.unesp.br
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pavan
authors.forename: Gustavo V
authors.initials: GV
authors.lastname: Poelhsitz
authors.forename: Lucas V P
authors.initials: LV
authors.lastname: da Cunha
authors.forename: Marilia I F
authors.initials: MI
authors.lastname: Barbosa
authors.forename: Sergio R A
authors.initials: SR
authors.lastname: Leite
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
authors.forename: Sang H
authors.initials: SH
authors.lastname: Cho
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.forename: Mariana S
authors.initials: MS
authors.lastname: de Camargo
authors.forename: Flávia A
authors.initials: FA
authors.lastname: Resende
authors.forename: Eliana A
authors.initials: EA
authors.lastname: Varanda
authors.forename: Clarice Q F
authors.initials: CQ
authors.lastname: Leite
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005260:Female; D006801:Humans; D007097:Imines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis / Q000187:drug effects; D009152:Mutagenicity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D010720:Phosphines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010848:Picolinic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*; D023382:Toxicity Tests, Acute
chemical_list: D000995:Antitubercular Agents; D056831:Coordination Complexes; D007097:Imines; D010720:Phosphines; D010848:Picolinic Acids; D012428:Ruthenium; C044646:phosphine; C030614:picolinic acid