6D1M

Design, synthesis, and X-ray of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects

6D1M の概要

• エントリーDOI: 10.2210/pdb6d1m/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 4-(cyclohexylselanyl)benzene-1-sulfonamide, ... (5 entities in total)
• 機能のキーワード: carbonic anhydrase inhibitors, neuropathic pain, selenium, metalloenzymes, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30083.15

構造登録者

Peat, T.S.,Angeli, A.,di Cesare Mannelli, L.,Micheli, L.,Ghelardini, C.,Supuran, C.T. (登録日: 2018-04-12, 公開日: 2018-06-13, 最終更新日: 2023-10-04)

主引用文献

Angeli, A.,di Cesare Mannelli, L.,Lucarini, E.,Peat, T.S.,Ghelardini, C.,Supuran, C.T.
Design, synthesis and X-ray crystallography of selenides bearing benzenesulfonamide moiety with neuropathic pain modulating effects.
Eur J Med Chem, 154:210-219, 2018

PubMed Abstract: A series of selenides bearing benzensulfonamide were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Potent inhibitory action, in the low nanomolar range, was detected against isoforms hCA II and VII, which are known to be involved in neuropathic pain modulation. These selenides showed on the other hand moderate inhibition against the cytosolic isoforms hCA I and transmembrane hCA IX. X-ray crystallographic data of two derivatives bound to hCA II allowed us to rationalize the excellent inhibitory data. In a mice model of neuropathic pain induced by oxaliplatin, some of the strong CA II/VII inhibitors induced a long lasting pain relieving effect.

PubMed: 29803994
DOI: 10.1016/j.ejmech.2018.05.026

実験手法

X-RAY DIFFRACTION (1.21 Å)