In Vitro and In Vivo Properties of CUO246, a Novel Bacterial DNA Gyrase/Topoisomerase IV Inhibitor

Autor: Johanne Blais, Charles R. Dean, Guillaume Lapointe, Jennifer A. Leeds, Sylvia Ma, Laura Morris, Heinz E. Moser, Colin S. Osborne, Katherine R. Prosen, Daryl Richie, Colin Skepper, Katherine Thompson, Jason Vo, Qin Yue, Alexey Rivkin

Publikováno v: Antimicrob Agents Chemother

CUO246, a novel DNA gyrase/topoisomerase IV inhibitor, is active in vitro against a broad range of Gram-positive, fastidious Gram-negative, and atypical bacterial pathogens and retains activity against quinolone-resistant strains in circulation. The

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d950dc498b15d26b8c411b490af69af6
https://doi.org/10.1128/aac.00921-22

Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria

Autor: David McKenney, Louis E. Metzger, Dirksen E. Bussiere, Sylvia Ma, Ashish Patel, Bhavesh Dhumale, Upendra Kulkarni, Jay Parthiban Lakshman, Sean King, Duncan Armstrong, Kyuto Tashiro, Lauren Kossy, Tushar Patel, Lauren M. Holder, Jogitha Selvarajah, Sarah Williams, Satya Yendluri, Colin Osborne, Jason Vo, Mangesh Fulsunder, Xiaolan Ling, Laura Wedel, Gianfranco De Pascale, Jennifer A. Leeds, Cody Cepura, Heinz E. Moser, Alexey Rivkin, Sunil Namballa, Colin K. Skepper, Bhavin Kantariya, Mina Mostafavi, Bhautik Savani, Anatoli Lvov, Guillaume Lapointe, Cornelia Bellamacina, Bhavesh Vora, Daryl L. Richie, Helen Chan, Wosenu Mergo, Jianwei Bian, Wei Shu, Keshav Mhaske, Aregahegn Yifru, Mark R. Sanderson, Swapnil Malekar, Johanne Blais, Qin Yue, Yong Zhang, Katherine V. Thompson, Julie Kim, Charles R. Dean, Vijay Sethuraman, Trixie Wagner, L. Mark Fisher, Dennis A. Veselkov, Darshit Patel, Folkert Reck, Jonas Noeske, Krishniah Vaarla, Lakhan Vala, Shailesh Satasia, Krunal Prajapati, Philippe Piechon, Valery Polyakov, Katherine R Prosen

Publikováno v: Lapointe, G, Skepper, C K, Holder, L M, Armstrong, D, Bellamacina, C, Blais, J, Bussiere, D, Bian, J, Cepura, C, Chan, H, Dean, C R, De Pascale, G, Dhumale, B, Fisher, L M, Fulsunder, M, Kantariya, B, Kim, J, King, S, Kossy, L, Kulkarni, U, Lakshman, J, Leeds, J A, Ling, X, Lvov, A, Ma, S, Malekar, S, McKenney, D, Mergo, W, Metzger, L, Mhaske, K, Moser, H E, Mostafavi, M, Namballa, S, Noeske, J, Osborne, C, Patel, A, Patel, D, Patel, T, Piechon, P, Polyakov, V, Prajapati, K, Prosen, K R, Reck, F, Richie, D L, Sanderson, M R, Satasia, S, Savani, B, Selvarajah, J, Sethuraman, V, Shu, W, Tashiro, K, Thompson, K V, Vaarla, K, Vala, L, Veselkov, D A, Vo, J, Vora, B, Wagner, T, Wedel, L, Williams, S L, Yendluri, S, Yue, Q, Yifru, A, Zhang, Y & Rivkin, A 2021, ' Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria ', Journal of Medicinal Chemistry, vol. 64, no. 9, pp. 6329-6357 . https://doi.org/10.1021/acs.jmedchem.1c00375

Herein, we describe the discovery and optimization of a novel series that inhibits bacterial DNA gyrase and topoisomerase IV via binding to, and stabilization of, DNA cleavage complexes. Optimization of this series led to the identification of compou

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56db96726415696056387173baa99222
https://kclpure.kcl.ac.uk/en/publications/675d57ab-71d9-4244-886c-019cc57306cd

Diagnosing antimicrobial resistance

Autor: Jean B. Patel, Jennifer A. Leeds, Carey-Ann D. Burnham, Justin O'Grady, Patrice Nordmann

Publikováno v: Nature Reviews Microbiology. 15:697-703

Antimicrobial resistance constitutes a global burden and is one of the major threats to public health. Although the emergence of resistant microorganisms is a natural phenomenon, the overuse or inappropriate use of antimicrobials has had a great effe

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24b1bbf8e2c775eada8301d0d4f16141
https://doi.org/10.1038/nrmicro.2017.103

Perspective on Antibacterial Lead Identification Challenges and the Role of Hypothesis-Driven Strategies

Autor: Cheryl L. Quinn, Jared A. Silverman, Jennifer A. Leeds, Lynn L. Silver, Laura McDowell

Publikováno v: SLAS discovery : advancing life sciences RD. 24(4)

For the past three decades, the pharmaceutical industry has undertaken many diverse approaches to discover novel antibiotics, with limited success. We have witnessed and personally experienced many mistakes, hurdles, and dead ends that have derailed

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a5cd3ec20f88a84fe1e86021f49b479
https://pubmed.ncbi.nlm.nih.gov/30890054

Advances and challenges in bacterial compound accumulation assays for drug discovery

Autor: Jennifer A. Leeds, David A. Six, Thomas Krucker

Publikováno v: Current opinion in chemical biology. 44

The identification of potent in vitro inhibitors of essential bacterial targets is relatively straightforward, however vanishingly few of these molecules have Gram-negative antibacterial potency and spectrum because of a failure to accumulate inside

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::684297abe5371b45083797c3c656662b
https://pubmed.ncbi.nlm.nih.gov/29803973