5WEX

Discovery of new selenoureido analogs of 4-(4-fluorophenylureido) benzenesulfonamides as carbonic anhydrase inhibitors

Summary for 5WEX

• Entry DOI: 10.2210/pdb5wex/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, GLYCEROL, ... (6 entities in total)
• Functional Keywords: carbonic anhydrase inhibitors, metalloenzymes, glutathione peroxidase, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29850.08

Authors

Angeli, A.,Tanini, D.,Peat, T.S.,Di Cesare Mannelli, L.,Bartolucci, G.,Capperucci, A.,Ghelardini, C.,Supuran, C.T.,Carta, F. (deposition date: 2017-07-10, release date: 2017-10-11, Last modification date: 2024-03-13)

Primary citation

Angeli, A.,Tanini, D.,Peat, T.S.,Di Cesare Mannelli, L.,Bartolucci, G.,Capperucci, A.,Ghelardini, C.,Supuran, C.T.,Carta, F.
Discovery of New Selenoureido Analogues of 4-(4-Fluorophenylureido)benzenesulfonamide as Carbonic Anhydrase Inhibitors.
ACS Med Chem Lett, 8:963-968, 2017

PubMed Abstract: A series of benzenesulfonamides bearing selenourea moieties was obtained considering the ureido-sulfonamide , in Phase I clinical trials as antitumor agent, as a lead molecule. All compounds showed interesting inhibition potencies against the physiologically relevant human (h) carbonic anhydrase (hCAs, EC 4.2.1.1) isoforms I, II, IV, and IX. The most flexible analogues in the series - showed low nanomolar inhibition constants against hCA I, II, and IX. We assessed selected compounds on the antioxidant properties and binding modes and evaluated human prostate (PC3), breast (MDA-MB-231), and colon-rectal (HT-29) cancer cell lines both in normoxic and hypoxic conditions.

PubMed: 28947945
DOI: 10.1021/acsmedchemlett.7b00280

Experimental method

X-RAY DIFFRACTION (1.26 Å)