8QUN
human carbonic anhydrase I in complex with 2-((5-cyano-4-hydroxy-6-(p-tolyl)pyrimidin-2-yl)thio)-N-(4-sulfamoylphenyl)acetamide
This is a non-PDB format compatible entry.
Summary for 8QUN
| Entry DOI | 10.2210/pdb8qun/pdb |
| Descriptor | Carbonic anhydrase 1, ZINC ION, 2-[5-cyano-4-(4-methylphenyl)-6-oxidanyl-pyrimidin-2-yl]sulfanyl-N-(4-sulfamoylphenyl)ethanamide, ... (6 entities in total) |
| Functional Keywords | carbonic anhydrase i; sulfonamide; metalloenzyme; inhibitor, lyase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 58955.33 |
| Authors | Angeli, A.,Ferraroni, M. (deposition date: 2023-10-16, release date: 2024-10-23, Last modification date: 2025-05-07) |
| Primary citation | Hefny, S.M.,El-Moselhy, T.F.,El-Din, N.,Ammara, A.,Angeli, A.,Ferraroni, M.,El-Dessouki, A.M.,Shaldam, M.A.,Yahya, G.,Al-Karmalawy, A.A.,Supuran, C.T.,Tawfik, H.O. A new framework for novel analogues of pazopanib as potent and selective human carbonic anhydrase inhibitors: Design, repurposing rational, synthesis, crystallographic, in vivo and in vitro biological assessments. Eur.J.Med.Chem., 274:116527-116527, 2024 Cited by PubMed Abstract: Herein, we describe the design and synthesis of novel aryl pyrimidine benzenesulfonamides APBSs 5a-n, 6a-c, 7a-b, and 8 as pazopanib analogues to explore new potent and selective inhibitors for the CA IX. All APBSs were examined in vitro for their promising inhibition activity against a small panel of hCAs (isoforms I, II, IX, and XII). The X-ray crystal structure of CA I in adduct with a representative APBS analogue was solved. APBS-5m, endowed with the best hCA IX inhibitory efficacy and selectivity, was evaluated for antiproliferative activity against a small panel of different cancer cell lines, SK-MEL-173, MDA-MB-231, A549, HCT-116, and HeLa, and it demonstrated one-digit IC values range from 2.93 μM (MDA-MB-231) to 5.86 μM (A549). Furthermore, compound APBS-5m was evaluated for its influence on hypoxia-inducible factor (HIF-1α) production, apoptosis induction, and colony formation in MDA-MB-231 cancer cells. The in vivo efficacy of APBS-5m as an antitumor agent was additionally investigated in an animal model of Solid Ehrlich Carcinoma (SEC). In order to offer perceptions into the conveyed hCA IX inhibitory efficacy and selectivity in silico, a molecular docking investigation was also carried out. PubMed: 38810335DOI: 10.1016/j.ejmech.2024.116527 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.606 Å) |
Structure validation
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