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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
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
Descripción
Sumario:[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.