Cell-based optimization of novel benzamides as potential antimalarial leads

Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan-kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its...

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Autores principales: Wu, Tao, Nagle, Advait, Sakata, Tomoyo, Henson, Kerstin, Borboa, Rachel, Chen, Zhong, Kuhen, Kelli, Plouffe, David, Winzeler, Elizabeth, Adrian, Francisco, Tuntland, Tove, Chang, Jonathan, Simerson, Susan, Howard, Steven, Ek, Jared, Isbell, John, Deng, Xianming, Gray, Nathanael S., Tully, David C., Chatterjee, Arnab K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Ltd 2009
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532596/
https://www.ncbi.nlm.nih.gov/pubmed/19879133
http://dx.doi.org/10.1016/j.bmcl.2009.10.050
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author Wu, Tao
Nagle, Advait
Sakata, Tomoyo
Henson, Kerstin
Borboa, Rachel
Chen, Zhong
Kuhen, Kelli
Plouffe, David
Winzeler, Elizabeth
Adrian, Francisco
Tuntland, Tove
Chang, Jonathan
Simerson, Susan
Howard, Steven
Ek, Jared
Isbell, John
Deng, Xianming
Gray, Nathanael S.
Tully, David C.
Chatterjee, Arnab K.
author_facet Wu, Tao
Nagle, Advait
Sakata, Tomoyo
Henson, Kerstin
Borboa, Rachel
Chen, Zhong
Kuhen, Kelli
Plouffe, David
Winzeler, Elizabeth
Adrian, Francisco
Tuntland, Tove
Chang, Jonathan
Simerson, Susan
Howard, Steven
Ek, Jared
Isbell, John
Deng, Xianming
Gray, Nathanael S.
Tully, David C.
Chatterjee, Arnab K.
author_sort Wu, Tao
collection PubMed
description Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan-kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its antiplasmodial activity. The evolution of this compound series leading to optimized candidates with good cellular potency against multiple strains as well as decent in vivo profile is described in this Letter.
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spelling pubmed-35325962012-12-31 Cell-based optimization of novel benzamides as potential antimalarial leads Wu, Tao Nagle, Advait Sakata, Tomoyo Henson, Kerstin Borboa, Rachel Chen, Zhong Kuhen, Kelli Plouffe, David Winzeler, Elizabeth Adrian, Francisco Tuntland, Tove Chang, Jonathan Simerson, Susan Howard, Steven Ek, Jared Isbell, John Deng, Xianming Gray, Nathanael S. Tully, David C. Chatterjee, Arnab K. Bioorg Med Chem Lett Article Screening our in-house compound collection using a cell based Plasmodium falciparum proliferation assay we discovered a known pan-kinase inhibitor scaffold as a hit. Further optimization of this series led us to a novel benzamide scaffold which was devoid of human kinase activity while retaining its antiplasmodial activity. The evolution of this compound series leading to optimized candidates with good cellular potency against multiple strains as well as decent in vivo profile is described in this Letter. Elsevier Science Ltd 2009-12-15 /pmc/articles/PMC3532596/ /pubmed/19879133 http://dx.doi.org/10.1016/j.bmcl.2009.10.050 Text en © 2009 Elsevier Ltd. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Wu, Tao
Nagle, Advait
Sakata, Tomoyo
Henson, Kerstin
Borboa, Rachel
Chen, Zhong
Kuhen, Kelli
Plouffe, David
Winzeler, Elizabeth
Adrian, Francisco
Tuntland, Tove
Chang, Jonathan
Simerson, Susan
Howard, Steven
Ek, Jared
Isbell, John
Deng, Xianming
Gray, Nathanael S.
Tully, David C.
Chatterjee, Arnab K.
Cell-based optimization of novel benzamides as potential antimalarial leads
title Cell-based optimization of novel benzamides as potential antimalarial leads
title_full Cell-based optimization of novel benzamides as potential antimalarial leads
title_fullStr Cell-based optimization of novel benzamides as potential antimalarial leads
title_full_unstemmed Cell-based optimization of novel benzamides as potential antimalarial leads
title_short Cell-based optimization of novel benzamides as potential antimalarial leads
title_sort cell-based optimization of novel benzamides as potential antimalarial leads
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532596/
https://www.ncbi.nlm.nih.gov/pubmed/19879133
http://dx.doi.org/10.1016/j.bmcl.2009.10.050
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