8BJX

Crystal structure of human Carbonic anhydrase II in complex with (R)-4-(3-(1-(6-nitropyridin-2-yl)pyrrolidin-3-yl)thioureido)benzenesulfonamide

This is a non-PDB format compatible entry.

Summary for 8BJX

• Entry DOI: 10.2210/pdb8bjx/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, 1-[(3~{R})-1-(6-nitropyridin-2-yl)pyrrolidin-3-yl]-3-(4-sulfamoylphenyl)thiourea, ... (6 entities in total)
• Functional Keywords: carbonic anhydrase ii; metalloenzyme; inhibitor, sulfonamide, lyase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 29947.18

Authors

Angeli, A.,Ferraroni, M. (deposition date: 2022-11-08, release date: 2023-11-22, Last modification date: 2026-03-04)

Primary citation

Angeli, A.,Micheli, L.,Carta, F.,Ferraroni, M.,Pirali, T.,Fernandez Carvajal, A.,Ferrer Montiel, A.,Di Cesare Mannelli, L.,Ghelardini, C.,Supuran, C.T.
First-in-Class Dual Hybrid Carbonic Anhydrase Inhibitors and Transient Receptor Potential Vanilloid 1 Agonists Revert Oxaliplatin-Induced Neuropathy.
J.Med.Chem., 66:1616-1633, 2023

PubMed Abstract: Here, we report for the first time a series of compounds potentially useful for the management of oxaliplatin-induced neuropathy (OINP) able to modulate the human Carbonic Anhydrases (hCAs) as well as the Transient Receptor Potential Vanilloid 1 (TRPV1). All compounds showed effective inhibition activity toward the main hCAs involved in such a pathology, whereas selected items reported moderate agonism of TRPV1. X-ray crystallographic experiments assessed the binding modes of the two enantiomers ()- and ()- within the hCA II cleft. Although the tails assumed diverse orientations, no appreciable effects were observed for their hCA II affinity. Similarly, the activity of ()- and ()- on TRPV1 was not influenced by the stereocenters. evaluation of the most promising derivatives ()-, ()-, and the two enantiomers ()-, ()- revealed antihypersensitivity effects in a mouse model of OINP with potent and persistent effect up to 75 min after administration.

PubMed: 36626645
DOI: 10.1021/acs.jmedchem.2c01911

Experimental method

X-RAY DIFFRACTION (1.283 Å)