6B59

Carbonic anhydrase II in complex with nitrogenous base-bearing benezenesulfonamide

6B59 の概要

• エントリーDOI: 10.2210/pdb6b59/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, 2-(6-amino-9H-purin-9-yl)-N-[2-(4-sulfamoylphenyl)ethyl]acetamide, ... (6 entities in total)
• 機能のキーワード: carbonic anhydrase, inhibitor, benzenesulfonamide, purine, adenine, lyase, lyase-inhibitor complex, 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: 29543.68

構造登録者

Lomelino, C.L.,McKenna, R.M. (登録日: 2017-09-28, 公開日: 2018-09-05, 最終更新日: 2023-10-04)

主引用文献

Nocentini, A.,Bua, S.,Lomelino, C.L.,McKenna, R.,Menicatti, M.,Bartolucci, G.,Tenci, B.,Di Cesare Mannelli, L.,Ghelardini, C.,Gratteri, P.,Supuran, C.T.
Discovery of New Sulfonamide Carbonic Anhydrase IX Inhibitors Incorporating Nitrogenous Bases.
ACS Med Chem Lett, 8:1314-1319, 2017

PubMed Abstract: Incorporation of the purine/pyrimidine moieties as tails to classical benzenesulfonamide scaffolds afforded two series of human (h) carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The compounds were designed according to the molecular hybridization approach, in order to modulate the interaction with different CA isozymes and exploit the antitumor effect of uracil and adenine derivatives in parallel and synergic mode to the inhibition of the tumor-associated hCA IX. The sulfonamides were investigated as inhibitors of four isoforms, cytosolic hCA I/II and transmembrane hCA IV/IX. The inhibitory profiles were dependent on the length and positioning of the spacer connecting the two pharmacophores. X-ray crystallography demonstrated the binding mode of an inhibitor to hCA II and hCA IX-mimic. Compounds endowed with the best hCA IX inhibitory efficacy were evaluated for antiproliferative activity against HT-29 colon cancer cell lines. The results suggest multiple mechanisms of action are responsible for the compounds' cytotoxic efficacy.

PubMed: 29259754
DOI: 10.1021/acsmedchemlett.7b00399

実験手法

X-RAY DIFFRACTION (1.638 Å)