Strong in vitro activities of two new rifabutin analogs against multidrug-resistant Mycobacterium tuberculosis.
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.
García
Ana-Belén
AB
Instituto Universitario de Química Organometálica Enrique Moles, Unidad Asociada al C.S.I.C., Universidad de Oviedo, c/ Julián Clavería 8, 33006 Oviedo, Spain.
Palacios
Juan J
JJ
Ruiz
María-Jesús
MJ
Barluenga
José
J
Aznar
Fernando
F
Cabal
María-Paz
MP
García
José María
JM
Díaz
Natalia
N
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*
D000904:Antibiotics, Antitubercular; D017828:Rifabutin