title: Strong in vitro activities of two new rifabutin analogs against multidrug-resistant Mycobacterium tuberculosis.
abstract: Two new rifabutin analogs, RFA-1 and RFA-2, show high in vitro antimycobacterial activities against Mycobacterium tuberculosis. MIC values of RFA-1 and RFA-2 were ≤0.02 μg/ml against rifamycin-susceptible strains and 0.5 μg/ml against a wide selection of multidrug-resistant strains, compared to ≥50 μg/ml for rifampin and 10 μg/ml for rifabutin. Molecular dynamic studies indicate that the compounds may exert tighter binding to mutants of RNA polymerase that have adapted to the rifamycins.
authors.affiliation: Instituto Universitario de Química Organometálica Enrique Moles, Unidad Asociada al C.S.I.C., Universidad de Oviedo, c/ Julián Clavería 8, 33006 Oviedo, Spain.
authors.forename: Ana-Belén
authors.initials: AB
authors.lastname: García
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Palacios
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Ruiz
authors.forename: José
authors.initials: J
authors.lastname: Barluenga
authors.forename: Fernando
authors.initials: F
authors.lastname: Aznar
authors.forename: María-Paz
authors.initials: MP
authors.lastname: Cabal
authors.forename: José María
authors.initials: JM
authors.lastname: García
authors.forename: Natalia
authors.initials: N
authors.lastname: Díaz
mesh_terms: D000904:Antibiotics, Antitubercular / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D017828:Rifabutin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000904:Antibiotics, Antitubercular; D017828:Rifabutin