6YOK
Para-Carborane di-propyl-sulfonamide in complex with CA IX mimic
Summary for 6YOK
| Entry DOI | 10.2210/pdb6yok/pdb |
| Related | 6YO2 6YO4 6YO7 6YOI |
| Descriptor | Carbonic anhydrase 2, ZINC ION, Para-Carborane di-propyl-sulfonamide, ... (4 entities in total) |
| Functional Keywords | carbonic anhydrase, ca inhibitor, lyase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29642.76 |
| Authors | Kugler, M.,Brynda, J.,Pospisilova, K.,Rezacova, P. (deposition date: 2020-04-14, release date: 2020-08-19, Last modification date: 2024-01-24) |
| Primary citation | Nekvinda, J.,Kugler, M.,Holub, J.,El Anwar, S.,Brynda, J.,Pospisilova, K.,Ruzickova, Z.,Rezacova, P.,Gruner, B. Direct Introduction of an Alkylsulfonamido Group on C-sites of Isomeric Dicarba-closo-dodecaboranes: The Influence of Stereochemistry on Inhibitory Activity against the Cancer-Associated Carbonic Anhydrase IX Isoenzyme. Chemistry, 26:16541-16553, 2020 Cited by PubMed Abstract: Carbonic anhydrase IX (CA IX), a tumor-associated metalloenzyme, represents a validated target for cancer therapy and diagnostics. Herein, we report the inhibition properties of isomeric families of sulfonamidopropyl-dicarba-closo-dodecaboranes group(s) prepared using a new direct five-step synthesis from the corresponding parent cages. The protocol offers a reliable solution for synthesis of singly and doubly substituted dicarba-closo-dodecaboranes with a different geometric position of carbon atoms. The closo-compounds from the ortho- and meta-series were then degraded to corresponding 11-vertex dicarba-nido-undecaborate(1-) anions. All compounds show in vitro enzymatic activity against CA IX in the low nanomolar or subnanomolar range. This is accompanied by clear isomer dependence of the inhibition constant (K ) and selectivity towards CA IX. Decreasing trends in K and selectivity index (S ) values are observed with increasing separation of the cage carbon atoms. Interactions of compounds with the active sites of CA IX were explored with X-ray crystallography, and eight high-resolution crystal structures uncovered the structural basis of inhibition potency and selectivity. PubMed: 32757220DOI: 10.1002/chem.202002809 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.25 Å) |
Structure validation
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