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Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors

A small library of 36 functionalized benzophenone thiosemicarbazone analogs has been prepared by chemical synthesis and evaluated for their ability to inhibit the cysteine proteases cathepsin L and cathepsin B. Inhibitors of cathepsins L and B have the potential to limit or arrest cancer metastasis....

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Autores principales: Kishore Kumar, G.D., Chavarria, Gustavo E., Charlton-Sevcik, Amanda K., Arispe, Wara M., MacDonough, Matthew T., Strecker, Tracy E., Chen, Shen-En, Siim, Bronwyn G., Chaplin, David J., Trawick, Mary Lynn, Pinney, Kevin G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125537/
https://www.ncbi.nlm.nih.gov/pubmed/20089402
http://dx.doi.org/10.1016/j.bmcl.2009.12.090
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author Kishore Kumar, G.D.
Chavarria, Gustavo E.
Charlton-Sevcik, Amanda K.
Arispe, Wara M.
MacDonough, Matthew T.
Strecker, Tracy E.
Chen, Shen-En
Siim, Bronwyn G.
Chaplin, David J.
Trawick, Mary Lynn
Pinney, Kevin G.
author_facet Kishore Kumar, G.D.
Chavarria, Gustavo E.
Charlton-Sevcik, Amanda K.
Arispe, Wara M.
MacDonough, Matthew T.
Strecker, Tracy E.
Chen, Shen-En
Siim, Bronwyn G.
Chaplin, David J.
Trawick, Mary Lynn
Pinney, Kevin G.
author_sort Kishore Kumar, G.D.
collection PubMed
description A small library of 36 functionalized benzophenone thiosemicarbazone analogs has been prepared by chemical synthesis and evaluated for their ability to inhibit the cysteine proteases cathepsin L and cathepsin B. Inhibitors of cathepsins L and B have the potential to limit or arrest cancer metastasis. The six most active inhibitors of cathepsin L (IC(50) < 85 nM) in this series incorporate a meta-bromo substituent in one aryl ring along with a variety of functional groups in the second aryl ring. These six analogs are selective for their inhibition of cathepsin L versus cathepsin B (IC(50) > 10,000 nM). The most active analog in the series, 3-bromophenyl-2′-fluorophenyl thiosemicarbazone 1, also efficiently inhibits cell invasion of the DU-145 human prostate cancer cell line.
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spelling pubmed-71255372020-04-08 Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors Kishore Kumar, G.D. Chavarria, Gustavo E. Charlton-Sevcik, Amanda K. Arispe, Wara M. MacDonough, Matthew T. Strecker, Tracy E. Chen, Shen-En Siim, Bronwyn G. Chaplin, David J. Trawick, Mary Lynn Pinney, Kevin G. Bioorg Med Chem Lett Article A small library of 36 functionalized benzophenone thiosemicarbazone analogs has been prepared by chemical synthesis and evaluated for their ability to inhibit the cysteine proteases cathepsin L and cathepsin B. Inhibitors of cathepsins L and B have the potential to limit or arrest cancer metastasis. The six most active inhibitors of cathepsin L (IC(50) < 85 nM) in this series incorporate a meta-bromo substituent in one aryl ring along with a variety of functional groups in the second aryl ring. These six analogs are selective for their inhibition of cathepsin L versus cathepsin B (IC(50) > 10,000 nM). The most active analog in the series, 3-bromophenyl-2′-fluorophenyl thiosemicarbazone 1, also efficiently inhibits cell invasion of the DU-145 human prostate cancer cell line. Elsevier Ltd. 2010-02-15 2010-01-06 /pmc/articles/PMC7125537/ /pubmed/20089402 http://dx.doi.org/10.1016/j.bmcl.2009.12.090 Text en Copyright © 2010 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Kishore Kumar, G.D.
Chavarria, Gustavo E.
Charlton-Sevcik, Amanda K.
Arispe, Wara M.
MacDonough, Matthew T.
Strecker, Tracy E.
Chen, Shen-En
Siim, Bronwyn G.
Chaplin, David J.
Trawick, Mary Lynn
Pinney, Kevin G.
Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors
title Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors
title_full Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors
title_fullStr Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors
title_full_unstemmed Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors
title_short Design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin L inhibitors
title_sort design, synthesis, and biological evaluation of potent thiosemicarbazone based cathepsin l inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125537/
https://www.ncbi.nlm.nih.gov/pubmed/20089402
http://dx.doi.org/10.1016/j.bmcl.2009.12.090
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