8CR0
Crystal structure of human carbonic anhydrase II in complex with a triazolyl benzoxaborole inhibitor
Summary for 8CR0
| Entry DOI | 10.2210/pdb8cr0/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, DIMETHYL SULFOXIDE, ... (5 entities in total) |
| Functional Keywords | benzoxaborole, boron, zinc enzyme, complex, lyase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29774.71 |
| Authors | Alterio, V.,De Simone, G.,Esposito, D. (deposition date: 2023-03-07, release date: 2023-06-21, Last modification date: 2024-02-07) |
| Primary citation | Nocentini, A.,Bonardi, A.,Bazzicalupi, C.,Alterio, V.,Esposito, D.,Monti, S.M.,Smietana, M.,De Simone, G.,Supuran, C.T.,Gratteri, P.,Winum, J.Y. 6-Substituted Triazolyl Benzoxaboroles as Selective Carbonic Anhydrase Inhibitors: In Silico Design, Synthesis, and X-ray Crystallography. J.Med.Chem., 66:8118-8129, 2023 Cited by PubMed Abstract: Benzoxaborole is currently a scaffold of great relevance in medicinal chemistry. In 2016, it was reported to be a new and valuable chemotype for designing carbonic anhydrase (CA) inhibitors. Herein, using an design, we report the synthesis and characterization of substituted 6-(1-1,2,3-triazol-1-yl)benzoxaboroles. 6-Azidobenzoxaborole was described for the first time as a molecular platform to prepare libraries of inhibitors by a copper(I)-catalyzed azide-alkyne cycloaddition a click chemistry strategy. With inhibition constants below 30 nM, some derivatives, such as compound , showed efficacy as selective hCA VII and IX inhibitors. The design hypothesis was validated by crystallographic investigation on the hCA II/ adduct, which provided explanations over the different inhibition behavior observed against the five evaluated hCA isoforms. Overall, this study identified as a new promising lead compound to develop novel anticancer agents targeting the tumor-associated hCA IX but also potent neuropathic pain relievers targeting hCA VII. PubMed: 37283561DOI: 10.1021/acs.jmedchem.3c00433 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.22 Å) |
Structure validation
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