8QQ9

human carbonic anhydrase I in complex with 1-benzyl-3-(1-hydroxy-3,4-dihydro-1H-benzo[c][1,2]oxaborinin-7-yl)thiourea

これはPDB形式変換不可エントリーです。

8QQ9 の概要

• エントリーDOI: 10.2210/pdb8qq9/pdb
• 分子名称: Carbonic anhydrase 1, ZINC ION, 1-[1,1-bis(oxidanyl)-3,4-dihydro-2,1$l^{4}-benzoxaborinin-7-yl]-3-(phenylmethyl)thiourea, ... (4 entities in total)
• 機能のキーワード: human carbonic anhydrase 1; metalloenzyme, inhibitor, benzoxaborine, boro, lyase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58601.59

構造登録者

Angeli, A.,Ferraroni, M. (登録日: 2023-10-04, 公開日: 2024-10-16, 最終更新日: 2025-04-16)

主引用文献

Giovannuzzi, S.,Nikitjuka, A.,Angeli, A.,Smietana, M.,Massardi, M.L.,Turati, M.,Ronca, R.,Bonardi, A.,Nocentini, A.,Ferraroni, M.,Supuran, C.T.,Winum, J.Y.
Benzoxaborinine, New Chemotype for Carbonic Anhydrase Inhibition: Ex Novo Synthesis, Crystallography, In Silico Studies, and Anti-Melanoma Cell Line Activity.
J.Med.Chem., 67:18221-18234, 2024

PubMed Abstract: The benzoxaborinine scaffold, a homologue of benzoxaborole with an additional carbon atom in the boracycle, shows significant potential in developing new therapeutic agents. This study reports the synthesis, inhibition assays against four human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, and anti-melanoma evaluation of 7-aryl(thio)ureido-substituted benzoxaborinines. Some derivatives, particularly compound , exhibited potent inhibitory activity (below 65 nM) against hCA IX and XII and stronger antiproliferative effects than on human melanoma cells under hypoxia. Crystallographic studies of benzoxaborinine adducts with hCA I and II demonstrated the binding mode of this chemotype, revealing that although both benzoxaborinine and benzoxaborole share a similar zinc-binding mode, the expanded ring in benzoxaborinine led to a different orientation within the active site. These findings suggest that benzoxaborinines hold promise for designing novel carbonic anhydrase inhibitors.

PubMed: 39378331
DOI: 10.1021/acs.jmedchem.4c01516

実験手法

X-RAY DIFFRACTION (2 Å)