6B5A
Carbonic anhydrase IX-mimic in complex with nitrogenous base-bearing benezenesulfonamide
Summary for 6B5A
| Entry DOI | 10.2210/pdb6b5a/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 2-(6-amino-9H-purin-9-yl)-N-[2-(4-sulfamoylphenyl)ethyl]acetamide, ... (4 entities in total) |
| Functional Keywords | carbonic anhydrase, inhibitor, benzenesulfonamide, purine, adenine, lyase, lyase-inhibitor complex, lyase/inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29285.28 |
| Authors | Lomelino, C.L.,McKenna, R.M. (deposition date: 2017-09-28, release date: 2018-09-05, Last modification date: 2023-10-04) |
| Primary citation | Nocentini, A.,Bua, S.,Lomelino, C.L.,McKenna, R.,Menicatti, M.,Bartolucci, G.,Tenci, B.,Di Cesare Mannelli, L.,Ghelardini, C.,Gratteri, P.,Supuran, C.T. Discovery of New Sulfonamide Carbonic Anhydrase IX Inhibitors Incorporating Nitrogenous Bases. ACS Med Chem Lett, 8:1314-1319, 2017 Cited by PubMed Abstract: Incorporation of the purine/pyrimidine moieties as tails to classical benzenesulfonamide scaffolds afforded two series of human (h) carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The compounds were designed according to the molecular hybridization approach, in order to modulate the interaction with different CA isozymes and exploit the antitumor effect of uracil and adenine derivatives in parallel and synergic mode to the inhibition of the tumor-associated hCA IX. The sulfonamides were investigated as inhibitors of four isoforms, cytosolic hCA I/II and transmembrane hCA IV/IX. The inhibitory profiles were dependent on the length and positioning of the spacer connecting the two pharmacophores. X-ray crystallography demonstrated the binding mode of an inhibitor to hCA II and hCA IX-mimic. Compounds endowed with the best hCA IX inhibitory efficacy were evaluated for antiproliferative activity against HT-29 colon cancer cell lines. The results suggest multiple mechanisms of action are responsible for the compounds' cytotoxic efficacy. PubMed: 29259754DOI: 10.1021/acsmedchemlett.7b00399 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.622 Å) |
Structure validation
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