Dioxane-Linked Amide Derivatives as Novel Bacterial Topoisomerase Inhibitors against Gram-Positive Staphylococcus aureus .

Autor:	Lu Y; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., Papa JL; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., Nolan S; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., English A; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., Seffernick JT; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., Shkolnikov N; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., Powell J; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., Lindert S; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., Wozniak DJ; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., Yalowich J; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States., Mitton-Fry MJ; Division of Medicinal Chemistry and Pharmacognosy.Division of Pharmaceutics and Pharmacology, Microbial Infection and Immunity, Department of Chemistry and Biochemistry, and Department of Microbiology, The Ohio State University, Columbus, Ohio 43210, United States.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2020 Oct 19; Vol. 11 (12), pp. 2446-2454. Date of Electronic Publication: 2020 Oct 19 (Print Publication: 2020).
DOI:	10.1021/acsmedchemlett.0c00428
Abstrakt:	In recent years, novel bacterial topoisomerase inhibitors (NBTIs) have been developed as future antibacterials for treating multidrug-resistant bacterial infections. A series of dioxane-linked NBTIs with an amide moiety has been synthesized and evaluated. Compound 3 inhibits DNA gyrase, induces the formation of single strand breaks to bacterial DNA, and achieves potent antibacterial activity against a variety of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Optimization of this series of analogues led to the discovery of a subseries of compounds ( 22 - 25 ) with more potent anti-MRSA activity, dual inhibition of DNA gyrase and topoisomerase IV, and the ability to induce double strand breaks through inhibition of S. aureus DNA gyrase. Competing Interests: The authors declare the following competing financial interest(s): M.M.F. is a shareholder of Pfizer, Inc. (© 2020 American Chemical Society.)
Databáze:	MEDLINE
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