1383370-95-3Relevant academic research and scientific papers
Hypoxia-targeting carbonic anhydrase IX inhibitors by a new series of nitroimidazole-sulfonamides/sulfamides/sulfamates
Rami, Marouan,Dubois, Ludwig,Parvathaneni, Nanda-Kumar,Alterio, Vincenzo,Van Kuijk, Simon J. A.,Monti, Simona Maria,Lambin, Philippe,De Simone, Giuseppina,Supuran, Claudiu T.,Winum, Jean-Yves
, p. 8512 - 8520 (2013/12/04)
A series of nitroimidazoles incorporating sulfonamide/sulfamide/sulfamate moieties were designed and synthesized as radio/chemosensitizing agent targeting the tumor-associated carbonic anhydrase (CA) isoforms IX and XII. Most of the new compounds were nanomolar inhibitors of these isoforms. Crystallographic studies on the complex of hCA II with the lead sulfamide derivative of this series clarified the binding mode of this type of inhibitors in the enzyme active site cavity. Some of the best nitroimidazole CA IX inhibitors showed significant activity in vitro by reducing hypoxia-induced extracellular acidosis in HT-29 and HeLa cell lines. In vivo testing of the lead molecule in the sulfamide series, in cotreatment with doxorubicin, demonstrated a chemosensitization of CA IX containing tumors. Such CA inhibitors, specifically targeting the tumor-associated isoforms, are candidates for novel treatment strategies against hypoxic tumors overexpressing extracellular CA isozymes.
CANCER TARGETING USING CARBONIC ANHYDRASE ISOFORM IX INHIBITORS
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Page/Page column 9-10, (2012/07/13)
The present invention concerns novel carbonic anhydrase IX inhibitors comprising a nitroimidazole moiety and their use in therapy of hypoxic conditions, in particular cancer treatment, especially chemotherapy and radiotherapy. The compounds of the invention have an increased specificity for the carbonic anhydrase IX enzyme compared to the art. The present invention relates to novel nitroimidazole derivates represented by formula (1).
