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

ACE inhibition enhances bradykinin relaxations through nitric oxide and B1 receptor activation in bovine coronary arteries

Autor: Cody Cepura, Kathryn M. Gauthier, William B. Campbell

Publikováno v: bchm. 394:1205-1212

Bradykinin causes vascular relaxations through release of endothelial relaxing factors including prostacyclin, nitric oxide (NO) and epoxyeicosatrienoic acids (EETs). Bradykinin is metabolized by angiotensin converting enzyme (ACE) and ACE inhibition

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1d4c5f7fd5f2d6e287f450cbbf4f5c06
https://doi.org/10.1515/hsz-2012-0348

Abstract 461: Macrophage 12/15-lipoxygenase Controls the Development of Experimental Hypertension through PPAR?

Autor: Tamas Kriska, Cody Cepura, Kathryn M. Gauthier, William B. Campbell

Publikováno v: Hypertension. 62

Targeted disruption of the 12/15-lipoxygenase (Alox15) gene in mice prevents the development of angiotensin II-, DOCA-salt-, and L-NAME-induced experimental hypertension. Macrophages are the primary source of Alox15. Using Alox15-/- and wild type (WT

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::36fb8858163cdf49fd6699b1c3b88aa4
https://doi.org/10.1161/hyp.62.suppl_1.a461

Mice lacking macrophage 12/15-lipoxygenase are resistant to experimental hypertension

Autor: Lawan Siangjong, Cody Cepura, William B. Campbell, Kathryn M. Gauthier, Devora Magier, Tamas Kriska

In mouse arteries, Alox15 [leukocyte-type 12/15-lipoxygenase (LO)] is assumed to regulate vascular function by metabolizing arachidonic acid (AA) to dilator eicosanoids that mediate the endothelium-dependent relaxations to AA and acetylcholine (ACh).

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36773791abb33bf32f80330db8e31334
https://europepmc.org/articles/PMC3378305/