Novel Lipophilic Acetohydroxamic Acid Derivatives Based on Conformationally Constrained Spiro Carbocyclic 2,6-Diketopiperazine Scaffolds with Potent Trypanocidal Activity

[Image: see text] We describe novel acetohydroxamic acid derivatives with potent activity against cultured bloodstream-form Trypanosoma brucei and selectivity indices of >1000. These analogues were derived from conformationally constrained, lipophilic, spiro carbocyclic 2,6-diketopiperazine (2,6-...

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Autores principales: Fytas, Christos, Zoidis, Grigoris, Tzoutzas, Nikolaos, Taylor, Martin C., Fytas, George, Kelly, John M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2011
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140774/
https://www.ncbi.nlm.nih.gov/pubmed/21542562
http://dx.doi.org/10.1021/jm200217m
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author Fytas, Christos
Zoidis, Grigoris
Tzoutzas, Nikolaos
Taylor, Martin C.
Fytas, George
Kelly, John M.
author_facet Fytas, Christos
Zoidis, Grigoris
Tzoutzas, Nikolaos
Taylor, Martin C.
Fytas, George
Kelly, John M.
author_sort Fytas, Christos
collection PubMed
description [Image: see text] We describe novel acetohydroxamic acid derivatives with potent activity against cultured bloodstream-form Trypanosoma brucei and selectivity indices of >1000. These analogues were derived from conformationally constrained, lipophilic, spiro carbocyclic 2,6-diketopiperazine (2,6-DKP) scaffolds by attaching acetohydroxamic acid moieties to the imidic nitrogen. Optimal activity was achieved by placing benzyl groups adjacent to the basic nitrogen of the 2,6-DKP core. S-Enantiomer 7d was the most active derivative against T. brucei (IC(50) = 6.8 nM) and T. cruzi (IC(50) = 0.21 μM).
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spelling pubmed-31407742011-07-21 Novel Lipophilic Acetohydroxamic Acid Derivatives Based on Conformationally Constrained Spiro Carbocyclic 2,6-Diketopiperazine Scaffolds with Potent Trypanocidal Activity Fytas, Christos Zoidis, Grigoris Tzoutzas, Nikolaos Taylor, Martin C. Fytas, George Kelly, John M. J Med Chem [Image: see text] We describe novel acetohydroxamic acid derivatives with potent activity against cultured bloodstream-form Trypanosoma brucei and selectivity indices of >1000. These analogues were derived from conformationally constrained, lipophilic, spiro carbocyclic 2,6-diketopiperazine (2,6-DKP) scaffolds by attaching acetohydroxamic acid moieties to the imidic nitrogen. Optimal activity was achieved by placing benzyl groups adjacent to the basic nitrogen of the 2,6-DKP core. S-Enantiomer 7d was the most active derivative against T. brucei (IC(50) = 6.8 nM) and T. cruzi (IC(50) = 0.21 μM). American Chemical Society 2011-05-04 2011-07-28 /pmc/articles/PMC3140774/ /pubmed/21542562 http://dx.doi.org/10.1021/jm200217m Text en Copyright © 2011 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org.
spellingShingle Fytas, Christos
Zoidis, Grigoris
Tzoutzas, Nikolaos
Taylor, Martin C.
Fytas, George
Kelly, John M.
Novel Lipophilic Acetohydroxamic Acid Derivatives Based on Conformationally Constrained Spiro Carbocyclic 2,6-Diketopiperazine Scaffolds with Potent Trypanocidal Activity
title Novel Lipophilic Acetohydroxamic Acid Derivatives Based on Conformationally Constrained Spiro Carbocyclic 2,6-Diketopiperazine Scaffolds with Potent Trypanocidal Activity
title_full Novel Lipophilic Acetohydroxamic Acid Derivatives Based on Conformationally Constrained Spiro Carbocyclic 2,6-Diketopiperazine Scaffolds with Potent Trypanocidal Activity
title_fullStr Novel Lipophilic Acetohydroxamic Acid Derivatives Based on Conformationally Constrained Spiro Carbocyclic 2,6-Diketopiperazine Scaffolds with Potent Trypanocidal Activity
title_full_unstemmed Novel Lipophilic Acetohydroxamic Acid Derivatives Based on Conformationally Constrained Spiro Carbocyclic 2,6-Diketopiperazine Scaffolds with Potent Trypanocidal Activity
title_short Novel Lipophilic Acetohydroxamic Acid Derivatives Based on Conformationally Constrained Spiro Carbocyclic 2,6-Diketopiperazine Scaffolds with Potent Trypanocidal Activity
title_sort novel lipophilic acetohydroxamic acid derivatives based on conformationally constrained spiro carbocyclic 2,6-diketopiperazine scaffolds with potent trypanocidal activity
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140774/
https://www.ncbi.nlm.nih.gov/pubmed/21542562
http://dx.doi.org/10.1021/jm200217m
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