9H0V
Human Carbonic Anhydrase II in complex with biguanide derivative inhibitor 1-carbamimidamido-N-[2-(4-sulfamoylphenyl)ethyl]methanimidamide
This is a non-PDB format compatible entry.
Summary for 9H0V
| Entry DOI | 10.2210/pdb9h0v/pdb |
| Descriptor | Carbonic anhydrase 2, ZINC ION, 1-carbamimidoyl-3-[2-(4-sulfamoylphenyl)ethyl]guanidine, ... (5 entities in total) |
| Functional Keywords | lyase, metalloenzyme, inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 30001.28 |
| Authors | |
| Primary citation | Melfi, F.,D'Agostino, I.,Carradori, S.,Carta, F.,Angeli, A.,Costa, G.,Renzi, G.,Cikos, A.,Vullo, D.,Resetar, J.,Ferraroni, M.,Baroni, C.,Mancuso, F.,Gitto, R.,Ambrosio, F.A.,Marchese, E.,Torcasio, R.,Amodio, N.,Capasso, C.,Alcaro, S.,Supuran, C.T. O-derivatization of natural tropolone and beta-thujaplicin leading to effective inhibitors of human carbonic anhydrases IX and XII. Eur.J.Med.Chem., 290:117552-117552, 2025 Cited by PubMed Abstract: Herein we report the chemical derivatization of the naturally occurring Tropolone (TRP) and its related compound β-Thujaplicin (β-TJP) as well as their in vitro assessment for inhibition of the physio/pathologically relevant hCAs isoforms I, II, VA; VII, IX and XII to obtain a first set of inhibition data useful for driving selected derivatives towards appropriate biomedical exploitation. The selected compound 17β was characterized for its chemical stability and assessed for its antiproliferative activity on a multiple myeloma model and showed potent pro-apoptotic features jointly with a safe toxicity profile on healthy cells. The binding mode of β-TJP within the hCA II was assessed by means of X-ray crystallography of the hCA II/β-TJP complex and showed almost complete superposition with the hCA II/TRP adduct reported in the literature. The data produced were used to elaborate a binding prediction model of such compounds on the hCAs VA, IX, and XII which are directly connected to important diseases. Overall, the achievements reported in this work are in the sustainment of the exploitation of naturally occurring troponoloid-based structures for biomedical purposes and thus contribute to the field in extending the variety of available chemical features. PubMed: 40179613DOI: 10.1016/j.ejmech.2025.117552 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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