1,3-Dioxane-Linked Novel Bacterial Topoisomerase Inhibitors: Expanding Structural Diversity and the Antibacterial Spectrum

被引：5

作者：

Lu, Yanran ^{[1
]}

Mann, Chelsea A. ^{[1
]}

Nolan, Sheri ^{[2
]}

Collins, Jessica A. ^{[3
]}

Parker, Elizabeth ^{[4
]}

Papa, Jonathan ^{[5
]}

Vibhute, Sandip ^{[1
]}

Jahanbakhsh, Seyedehameneh ^{[6
]}

Thwaites, Mary ^{[6
]}

Hufnagel, David ^{[6
]}

Hazbon, Manzour H. ^{[7
]}

Moreno, Jane ^{[7
]}

Stedman, Timothy T. ^{[7
]}

Wittum, Thomas ^{[4
]}

Wozniak, Daniel J. ^{[2
,8
]}

Osheroff, Neil ^{[3
,9
,10
]}

Yalowich, Jack C. ^{[5
]}

Mitton-Fry, Mark J. ^{[1
]}

机构：

[1] Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA

[2] Ohio State Univ, Coll Med, Microbial Infect & Immun, Columbus, OH 43210 USA

[3] Vanderbilt Univ, Dept Biochem, Sch Med, Nashville, TN 37232 USA

[4] Ohio State Univ, Coll Vet Med, Dept Vet Prevent Med, Columbus, OH 43210 USA

[5] Ohio State Univ, Coll Pharm, Div Pharmaceut & Pharmacol, Columbus, OH 43210 USA

[6] Micromyx, Kalamazoo, MI 49008 USA

[7] ATCC, Manassas, VA 20110 USA

[8] Ohio State Univ, Coll Arts & Sci, Dept Microbiol, Columbus, OH 43210 USA

[9] Vanderbilt Univ, Dept Med Hematol Oncol, Sch Med, Nashville, TN 37232 USA

[10] VA Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2022年 / 13卷 / 06期

关键词：

MRSA; gonorrhea; antibacterial; gyrase; TopoIV; hERG; POTENT INHIBITORS; TRICYCLICS E.G; DERIVATIVES; MECHANISM; BROAD; SAR;

D O I：

10.1021/acsmedchemlett.2c00111

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Antibacterial resistance continues its devastation of available therapies. Novel bacterial topoisomerase inhibitors (NBTIs) offer one solution to this critical issue. Two series of amine NBTIs bearing tricyclic DNA-binding moieties as well as amide NBTIs with a bicyclic DNA-binding moiety were synthesized and evaluated against methicillin-resistant Staphylococcus aureus (MRSA). Additionally, these compounds and a series of bicyclic amine analogues displayed high activity against susceptible and drug-resistant Neisseria gonorrhoeae, expanding the spectrum of these dioxane-linked NBTIs.

引用

页码：955 / 963

页数：9

共 38 条

[1] Mechanism of Quinolone Action and Resistance
Aldred, Katie J.
Kerns, Robert J.
Osheroff, Neil
[J]. BIOCHEMISTRY, 2014, 53 (10) : 1565 - 1574
[2] [Anonymous], 2016, M45: Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria
[3] [Anonymous], 2018, M07 CLSI
[4] [Anonymous], 2019, ANTIBIOTIC RESISTANC
[5] Type IIA topoisomerase inhibition by a new class of antibacterial agents
Bax, Benjamin D.
Chan, Pan F.
Eggleston, Drake S.
Fosberry, Andrew
Gentry, Daniel R.
Gorrec, Fabrice
Giordano, Ilaria
Hann, Michael M.
Hennessy, Alan
Hibbs, Martin
Huang, Jianzhong
Jones, Emma
Jones, Jo
Brown, Kristin Koretke
Lewis, Ceri J.
May, Earl W.
Saunders, Martin R.
Singh, Onkar
Spitzfaden, Claus E.
Shen, Carol
Shillings, Anthony
Theobald, Andrew J.
Wohlkonig, Alexandre
Pearson, Neil D.
Gwynn, Michael N.
[J]. NATURE, 2010, 466 (7309) : 935 - U51
[6] Charrier C, 2017, ANTIMICROB AGENTS CH, V61, DOI [10.1128/aac.02100-16, 10.1128/AAC.02100-16]
[7] Antibacterial activity of novel dual bacterial DNA type II topoisomerase inhibitors
D'Atanasio, Noemi
de Joannon, Alessandra Capezzone
Di Sante, Laura
Mangano, Giorgina
Ombrato, Rosella
Vitiello, Marco
Bartella, Cristina
Magaro, Gabriele
Prati, Federica
Milanese, Claudio
Vignaroli, Carla
Di Giorgio, Francesco Paolo
Tongiani, Serena
[J]. PLOS ONE, 2020, 15 (02):
[8] Farrell DJ, 2017, ANTIMICROB AGENTS CH, V61, DOI [10.1128/aac.02047-16, 10.1128/AAC.02047-16]
[9] Bimodal Actions of a Naphthyridone/Aminopiperidine-Based Antibacterial That Targets Gyrase and Topoisomerase IV
Gibson, Elizabeth G.
Oviatt, Alexandria A.
Cacho, Monica
Neuman, Keir C.
Chan, Pan F.
Osheroff, Neil
[J]. BIOCHEMISTRY, 2019, 58 (44) : 4447 - 4455
[10] Mechanistic and Structural Basis for the Actions of the Antibacterial Gepotidacin against Staphylococcus aureus Gyrase
Gibson, Elizabeth G.
Bax, Ben
Chan, Pan F.
Osheroff, Neil
[J]. ACS INFECTIOUS DISEASES, 2019, 5 (04): : 570 - 581

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