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N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms
[Image: see text] A series of N-acylbenzenesulfonamide dihydro-1,3,4-oxadiazole hybrids (EMAC8000a–m) was designed and synthesized with the aim to target tumor associated carbonic anhydrase (hCA) isoforms IX and XII. Most of the compounds were selective inhibitors of the tumor associated hCA XII. Mo...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554910/ https://www.ncbi.nlm.nih.gov/pubmed/28835790 http://dx.doi.org/10.1021/acsmedchemlett.7b00205 |
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author | Bianco, Giulia Meleddu, Rita Distinto, Simona Cottiglia, Filippo Gaspari, Marco Melis, Claudia Corona, Angela Angius, Rossella Angeli, Andrea Taverna, Domenico Alcaro, Stefano Leitans, Janis Kazaks, Andris Tars, Kaspars Supuran, Claudiu T. Maccioni, Elias |
author_facet | Bianco, Giulia Meleddu, Rita Distinto, Simona Cottiglia, Filippo Gaspari, Marco Melis, Claudia Corona, Angela Angius, Rossella Angeli, Andrea Taverna, Domenico Alcaro, Stefano Leitans, Janis Kazaks, Andris Tars, Kaspars Supuran, Claudiu T. Maccioni, Elias |
author_sort | Bianco, Giulia |
collection | PubMed |
description | [Image: see text] A series of N-acylbenzenesulfonamide dihydro-1,3,4-oxadiazole hybrids (EMAC8000a–m) was designed and synthesized with the aim to target tumor associated carbonic anhydrase (hCA) isoforms IX and XII. Most of the compounds were selective inhibitors of the tumor associated hCA XII. Moreover, resolution of EMAC8000d racemic mixture led to the isolation of the levorotatory eutomer exhibiting an increase of hCA XII inhibition potency and selectivity with respect to hCA II. Computational studies corroborated these data. Overall our data indicate that both substitution pattern and stereochemistry of dihydro-1,3,4-oxadiazole could be considered as key factors to determine activity and selectivity toward hCA isozymes. These results can provide further indication for the design and optimization of selective hCA inhibitors. |
format | Online Article Text |
id | pubmed-5554910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-55549102017-08-23 N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms Bianco, Giulia Meleddu, Rita Distinto, Simona Cottiglia, Filippo Gaspari, Marco Melis, Claudia Corona, Angela Angius, Rossella Angeli, Andrea Taverna, Domenico Alcaro, Stefano Leitans, Janis Kazaks, Andris Tars, Kaspars Supuran, Claudiu T. Maccioni, Elias ACS Med Chem Lett [Image: see text] A series of N-acylbenzenesulfonamide dihydro-1,3,4-oxadiazole hybrids (EMAC8000a–m) was designed and synthesized with the aim to target tumor associated carbonic anhydrase (hCA) isoforms IX and XII. Most of the compounds were selective inhibitors of the tumor associated hCA XII. Moreover, resolution of EMAC8000d racemic mixture led to the isolation of the levorotatory eutomer exhibiting an increase of hCA XII inhibition potency and selectivity with respect to hCA II. Computational studies corroborated these data. Overall our data indicate that both substitution pattern and stereochemistry of dihydro-1,3,4-oxadiazole could be considered as key factors to determine activity and selectivity toward hCA isozymes. These results can provide further indication for the design and optimization of selective hCA inhibitors. American Chemical Society 2017-06-21 /pmc/articles/PMC5554910/ /pubmed/28835790 http://dx.doi.org/10.1021/acsmedchemlett.7b00205 Text en Copyright © 2017 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Bianco, Giulia Meleddu, Rita Distinto, Simona Cottiglia, Filippo Gaspari, Marco Melis, Claudia Corona, Angela Angius, Rossella Angeli, Andrea Taverna, Domenico Alcaro, Stefano Leitans, Janis Kazaks, Andris Tars, Kaspars Supuran, Claudiu T. Maccioni, Elias N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms |
title | N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole
Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms |
title_full | N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole
Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms |
title_fullStr | N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole
Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms |
title_full_unstemmed | N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole
Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms |
title_short | N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole
Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms |
title_sort | n-acylbenzenesulfonamide dihydro-1,3,4-oxadiazole
hybrids: seeking selectivity toward carbonic anhydrase isoforms |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554910/ https://www.ncbi.nlm.nih.gov/pubmed/28835790 http://dx.doi.org/10.1021/acsmedchemlett.7b00205 |
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