8OTP

Crystal structure of human carbonic anhydrase II with 1-cyclopropyl-6-fluoro-4-oxo-7-(4-(4-sulfamoylbenzoyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid

これはPDB形式変換不可エントリーです。

8OTP の概要

• エントリーDOI: 10.2210/pdb8otp/pdb
• 分子名称: Carbonic anhydrase 2, ZINC ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: carbonic anhydrase ii, sulfonamide, metalloenzyme, ciprofloxacin, lyase
• 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: 29961.09

構造登録者

Angeli, A.,Ferraroni, M. (登録日: 2023-04-21, 公開日: 2024-05-01, 最終更新日: 2024-11-27)

主引用文献

Marinacci, B.,D'Agostino, I.,Angeli, A.,Carradori, S.,Melfi, F.,Grande, R.,Corsiani, M.,Ferraroni, M.,Agamennone, M.,Tondo, A.R.,Zara, S.,Puca, V.,Pellegrini, B.,Vagaggini, C.,Dreassi, E.,Patrauchan, M.A.,Capasso, C.,Nicolotti, O.,Carta, F.,Supuran, C.T.
Inhibition of Pseudomonas aeruginosa Carbonic Anhydrases, Exploring Ciprofloxacin Functionalization Toward New Antibacterial Agents: An In-Depth Multidisciplinary Study.
J.Med.Chem., 67:19077-19102, 2024

PubMed Abstract: Ciprofloxacin (CPX) is one of the most employed antibiotics in clinics to date. However, the rise of drug-resistant bacteria is dramatically impairing its efficacy, especially against life-threatening pathogens, such as . This Gram-negative bacterium is an opportunistic pathogen, often infecting immuno-compromised patients with severe or fatal outcomes. The evidence of the possibility of exploiting Carbonic Anhydrase (CA, EC: 4.2.1.1) enzymes as pharmacological targets along with their role in virulence inspired the derivatization of CPX with peculiar CA-inhibiting chemotypes. Thus, a large library of CPX derivatives was synthesized and tested on a panel of bacterial CAs and human isoenzymes I and II. Selected derivatives were evaluated for antibacterial activity, revealing bactericidal and antibiofilm properties for some compounds. Importantly, promising preliminary absorption, distribution, metabolism, and excretion (ADME) properties were found and no cytotoxicity was detected for some representative compounds when tested in larvae.

PubMed: 39453626
DOI: 10.1021/acs.jmedchem.4c01555

実験手法

X-RAY DIFFRACTION (1.4 Å)