1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics against Multidrug-Resistant Acinetobacter baumannii

详细信息    查看全文

• 作者：William M. Huggins ; Bradley M. Minrovic ; Brendan W. Corey ; Anna C. Jacobs ; Roberta J. Melander ; Roger D. Sommer ; Daniel V. Zurawski ; Christian Melander
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：January 12, 2017
• 年：2017
• 卷：8
• 期：1
• 页码：27-31
• 全文大小：274K
• ISSN：1948-5875

文摘

With only two new classes of antibiotics developed in the last 40 years, novel antibiotics are desperately needed to combat the growing problem of multidrug-resistant and extensively drug resistant bacteria, particularly Gram-negative bacteria. Described in this letter is the synthesis and antibiotic activity of 1,2,4-triazolidine-3-thiones as narrow spectrum antibiotics. Optimization of the 1,2,4-triazolidine-3-thione scaffold identified a small molecule with potent antibiotic activity against multiple strains of multidrug-resistant and extensively drug-resistant Acinetobacter baumannii. This small molecule also shows single dose, in vivo activity in a Galleria mellonella infection model with A. baumannii and represents a promising start in the development of a class of drugs that can target this bacterial pathogen.