Strong In Vitro Activities of Two New Rifabutin Analogs against Multidrug-Resistant Mycobacterium tuberculosis

被引：8

作者：

Garcia, Ana-Belen ^{[1
]}

Palacios, Juan J. ^{[2
]}

Ruiz, Maria-Jesus ^{[3
]}

Barluenga, Jose ^{[1
]}

Aznar, Fernando ^{[1
]}

Cabal, Maria-Paz ^{[1
]}

Maria Garcia, Jose ^{[4
]}

Diaz, Natalia ^{[5
]}

机构：

[1] Univ Oviedo, Unidad Asociada, Inst Univ Quim Organomet Enrique Moles, CSIC, E-33006 Oviedo, Spain

[2] Hosp Univ Cent Asturias, Unidad Referencia Reg Micobacterias, Oviedo 33006, Spain

[3] Hosp Gen Univ Gregorio Maranon, Serv Microbiol Clin, Madrid, Spain

[4] Hosp San Agustin, Serv Neumol, Aviles 33400, Spain

[5] Univ Oviedo, Dept Quim Fis & Analit, Oviedo 33006, Spain

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2010年 / 54卷 / 12期

关键词：

RIFAMYCINS; DRUGS;

D O I：

10.1128/AAC.00149-10

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 mu g/ml against rifamycin-susceptible strains and 0.5 mu g/ml against a wide selection of multidrug-resistant strains, compared to >= 50 mu g/ml for rifampin and 10 mu g/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.

引用

页码：5363 / 5365

页数：3

共 17 条

[1]

[Anonymous], 2008, GLOBAL TUBERCULOSIS

[2]

[Anonymous], 2003, M24A NAT COMM CLIN L

[3]

BARLUENGA J, 2007, Patent No. 7521458

[4]

BARLUENGA J, 2007, Patent No. 1783129

[5] New rifabutin analogs:: Synthesis and biological activity against Mycobacterium tuberculosis [J].

Barluenga, Jose ;

Aznar, Fernando ;

Garcia, Ana-Belen ;

Cabal, Maria-Paz ;

Palacios, Juan J. ;

Menendez, Maria-Angela .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (22) :5717-5722

[6]

Bryskier A, 2005, ANTIMICROBIAL AGENTS: ANTIBACTERIALS AND ANTIFUNGALS, pXXVII

[7] Structural, functional, and genetic analysis of sorangicin inhibition of bacterial RNA polymerase [J].

Campbell, EA ;

Pavlova, O ;

Zenkin, N ;

Leon, F ;

Irschik, H ;

Jansen, R ;

Severinov, K ;

Darst, SA .

EMBO JOURNAL, 2005, 24 (04) :674-682

[8] The growing burden of tuberculosis - Global trends and interactions with the HIV epidemic [J].

Corbett, EL ;

Watt, CJ ;

Walker, N ;

Maher, D ;

Williams, BG ;

Raviglione, MC ;

Dye, C .

ARCHIVES OF INTERNAL MEDICINE, 2003, 163 (09) :1009-1021

[9] Worldwide incidence of multidrug-resistant tuberculosis [J].

Dye, C ;

Espinal, MA ;

Watt, CJ ;

Mbiaga, C ;

Williams, BG .

JOURNAL OF INFECTIOUS DISEASES, 2002, 185 (08) :1197-1202

[10] Rifamycin-mode of action, resistance, and biosynthesis [J].

Floss, HG ;

Yu, TW .

CHEMICAL REVIEWS, 2005, 105 (02) :621-632

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