8R2K
Human Carbonic Anhydrase II in complex with 4-((2-oxo-5-(3,4,5-trimethoxyphenyl)-2,5-dihydrofuran-3-yl)amino)benzenesulfonamide
This is a non-PDB format compatible entry.
Summary for 8R2K
| Entry DOI | 10.2210/pdb8r2k/pdb |
| Descriptor | Carbonic anhydrase 2, GLYCEROL, ZINC ION, ... (5 entities in total) |
| Functional Keywords | carbonic anhydrase ii; metalloenzyme; sulfonamide; inhibitor, lyase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29867.00 |
| Authors | Angeli, A.,Ferraroni, M. (deposition date: 2023-11-06, release date: 2024-11-13, Last modification date: 2025-05-28) |
| Primary citation | Al-Matarneh, C.M.,Pinteala, M.,Nicolescu, A.,Silion, M.,Mocci, F.,Puf, R.,Angeli, A.,Ferraroni, M.,Supuran, C.T.,Zara, S.,Carradori, S.,Paoletti, N.,Bonardi, A.,Gratteri, P. Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety. J.Med.Chem., 67:3018-3038, 2024 Cited by PubMed Abstract: New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure-reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations ( 3.9-870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX ( 1.9-211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment. PubMed: 38301036DOI: 10.1021/acs.jmedchem.3c02190 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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