Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship

被引:6
作者
Gao, Rui [1 ]
Liao, Sha [2 ]
Zhang, Chen [1 ]
Zhu, Weilong [1 ]
Wang, Liyan [2 ]
Huang, Jin [2 ]
Zhao, Zhenjiang [2 ]
Li, Honglin [2 ]
Qian, Xuhong [1 ]
Xu, Yufang [1 ]
机构
[1] E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China
[2] E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China
基金
中国国家自然科学基金;
关键词
Carbonic anhydrase inhibitors; Benzenesulfonamides; Structure-activity relationship; Molecular docking; RAY CRYSTALLOGRAPHIC STRUCTURE; HUMAN ISOZYME-II; SULFONAMIDES; DESIGN; TARGET; PH; ACTIVATORS; ANTITUMOR; ACIDOSIS; GROWTH;
D O I
10.1016/j.ejmech.2013.01.030
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In this study, starting from a lead compound discovered by virtual screening, a series of novel hetero-cyclic substituted benzenesulfonamides were designed and synthesized as new carbonic anhydrase IX (CA IX) inhibitors. Some compounds exhibited potent inhibitory effects against CA IX (in the low nanomolar range) as well as high selectivity against other carbonic anhydrase isozymes (CA I and CA II). The most potent and selective compound 27 could inhibit CA IX in the subnanomolar level with IC50 of 0.48 nM, which increased the potency by about 40-fold against CA IX compared with the lead compound 26, and presented more than 10(3) fold selectivity over CA I and CA II. The structure activity relationship (SAR) based on the docking experiments further elucidated the effects of the compounds on the bioactivity and selectivity. (C) 2013 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:597 / 604
页数:8
相关论文
共 31 条
[1]   Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the perfluorobenzoyl analogue of methazolamide. Implications for the drug design of fluorinated inhibitors [J].
Abbate, F ;
Casini, A ;
Scozzafava, A ;
Supuran, CT .
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2003, 18 (04) :303-308
[2]  
Alterio V., 2009, DRUG DESIGN ZINC ENZ, P73
[3]   Multiple Binding Modes of Inhibitors to Carbonic Anhydrases: How to Design Specific Drugs Targeting 15 Different Isoforms? [J].
Alterio, Vincenzo ;
Di Fiore, Anna ;
D'Ambrosio, Katia ;
Supuran, Claudiu T. ;
De Simone, Giuseppina .
CHEMICAL REVIEWS, 2012, 112 (08) :4421-4468
[4]   Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with a bis-sulfonamide - Two heads are better than one? [J].
Casini, A ;
Abbate, F ;
Scozzafava, A ;
Supuran, CT .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (16) :2759-2763
[5]   Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer [J].
Chiche, Johanna ;
Brahimi-Horn, M. Christiane ;
Pouyssegur, Jacques .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2010, 14 (04) :771-794
[6]   Hypoxia-Inducible Carbonic Anhydrase IX and XII Promote Tumor Cell Growth by Counteracting Acidosis through the Regulation of the Intracellular pH [J].
Chiche, Johanna ;
Ilc, Karine ;
Laferriere, Julie ;
Trottier, Eric ;
Dayan, Frederic ;
Mazure, Nathalie M. ;
Brahimi-Horn, M. Christiane ;
Pouyssegur, Jacques .
CANCER RESEARCH, 2009, 69 (01) :358-368
[7]   A perspective on quantitative structure-activity relationships and carbonic anhydrase inhibitors [J].
Clare, Brian W. ;
Supuran, Claudiu. T. .
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2006, 2 (01) :113-137
[8]   Antiobesity carbonic anhydrase inhibitors [J].
De Simone, Giuseppina ;
Supuran, Claudiu T. .
CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2007, 7 (09) :879-884
[9]   QUANTITATIVE PREPARATION OF CHLORO- AND BROMOPHTHALAZINES [J].
HIRSCH, A ;
ORPHANOS, D .
CANADIAN JOURNAL OF CHEMISTRY, 1965, 43 (10) :2708-&
[10]   Synthesis of new acylsulfamoyl benzoxaboroles as potent inhibitors of HCV NS3 protease [J].
Li, Xianfeng ;
Zhang, Yong-Kang ;
Liu, Yang ;
Zhang, Suoming ;
Ding, Charles Z. ;
Zhou, Yasheen ;
Plattner, Jacob J. ;
Baker, Stephen J. ;
Liu, Liang ;
Bu, Wei ;
Kazmierski, Wieslaw M. ;
Wright, Lois L. ;
Smith, Gary K. ;
Jarvest, Richard L. ;
Duan, Maosheng ;
Ji, Jing-Jing ;
Cooper, Joel P. ;
Tallant, Matthew D. ;
Crosby, Renae M. ;
Creech, Katrina ;
Ni, Zhi-Jie ;
Zou, Wuxin ;
Wright, Jon .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (24) :7493-7497