| Literature DB >> 28291943 |
Shajila Siricilla1, Katsuhiko Mitachi1, Junshu Yang2, Shakiba Eslamimehr1, Maddie R Lemieux1, Bernd Meibohm1, Yinduo Ji2, Michio Kurosu1.
Abstract
Multidrug-resistant (MDR) Acinetobacter baumannii is one of the most difficult Gram-negative bacteria to treat and eradicate. In a cell-based screening of pleuromutilin derivatives against a drug sensitive A. baumannii strain, new molecules (2-4) exhibit bacteriostatic activity with 3.13 μg/mL concentration and 1 shows bactericidal activity with an MBC of 6.25 μg/mL. The pleuromutilin derivative 1 displays strong synergistic effects with doxycycline in a wide range of concentrations. A 35/1 ratio of 1 and doxycycline (1-Dox 35/1) kills drug susceptible A. baumannii with the MBC of 2.0 μg/mL and an MDR A. baumannii with the MBC of 3.13 μg/mL. In vitro anti-Acinetobacter activity of 1-Dox 35/1 is superior to that of clinical drugs such as tobramycin, tigecycline, and colistin. The efficacy of 1-Dox 35/1 is evaluated in a mouse septicemia model; treatment of the infected C57BL/6 mice with 1-Dox 35/1 protects from lethal infection of A. baumannii with an ED50 value of <2.0 mg/kg.Entities:
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Year: 2017 PMID： 28291943 PMCID： PMC5469366 DOI： 10.1021/acs.jmedchem.6b01805
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446