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1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics against Multidrug-Resistant Acinetobacter baumannii.
ACS Med Chem Lett. 2017 Jan 12; 8(1):27-31.AM

Abstract

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.

Authors+Show Affiliations

Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.Wound Infections Department, Walter Reed Army Institute of Research , Silver Spring, Maryland 20910, United States.Wound Infections Department, Walter Reed Army Institute of Research , Silver Spring, Maryland 20910, United States.Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.Wound Infections Department, Walter Reed Army Institute of Research , Silver Spring, Maryland 20910, United States.Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28105270

Citation

Huggins, William M., et al. "1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics Against Multidrug-Resistant Acinetobacter Baumannii." ACS Medicinal Chemistry Letters, vol. 8, no. 1, 2017, pp. 27-31.
Huggins WM, Minrovic BM, Corey BW, et al. 1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics against Multidrug-Resistant Acinetobacter baumannii. ACS Med Chem Lett. 2017;8(1):27-31.
Huggins, W. M., Minrovic, B. M., Corey, B. W., Jacobs, A. C., Melander, R. J., Sommer, R. D., Zurawski, D. V., & Melander, C. (2017). 1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics against Multidrug-Resistant Acinetobacter baumannii. ACS Medicinal Chemistry Letters, 8(1), 27-31. https://doi.org/10.1021/acsmedchemlett.6b00296
Huggins WM, et al. 1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics Against Multidrug-Resistant Acinetobacter Baumannii. ACS Med Chem Lett. 2017 Jan 12;8(1):27-31. PubMed PMID: 28105270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics against Multidrug-Resistant Acinetobacter baumannii. AU - Huggins,William M, AU - Minrovic,Bradley M, AU - Corey,Brendan W, AU - Jacobs,Anna C, AU - Melander,Roberta J, AU - Sommer,Roger D, AU - Zurawski,Daniel V, AU - Melander,Christian, Y1 - 2016/11/12/ PY - 2016/07/29/received PY - 2016/10/31/accepted PY - 2017/1/21/entrez PY - 2017/1/21/pubmed PY - 2017/1/21/medline KW - Acinetobacter baumannii KW - antibiotic resistance KW - antibiotics SP - 27 EP - 31 JF - ACS medicinal chemistry letters JO - ACS Med Chem Lett VL - 8 IS - 1 N2 - 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. SN - 1948-5875 UR - https://www.unboundmedicine.com/medline/citation/28105270/124_Triazolidine_3_thiones_as_Narrow_Spectrum_Antibiotics_against_Multidrug_Resistant_Acinetobacter_baumannii_ L2 - https://dx.doi.org/10.1021/acsmedchemlett.6b00296 DB - PRIME DP - Unbound Medicine ER -
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