Discovery of 1,1鈥?Biphenyl-4-sulfonamides as a New Class of Potent and Selective Carbonic Anhydrase XIV Inhibitors
详细信息 查看全文
- 作者：Giuseppe La Regina ; Antonio Coluccia ; Valeria Famiglini ; Sveva Pelliccia ; Ludovica Monti ; Daniela Vullo ; Elisa Nuti ; Vincenzo Alterio ; Giuseppina De Simone ; Simona Maria Monti ; Peiwen Pan ; Seppo Parkkila ; Claudiu T. Supuran ; Armando Rossello ; Romano Silvestri
- 刊名：Journal of Medicinal Chemistry
- 出版年：2015
- 出版时间：November 12, 2015
- 年：2015
- 卷：58
- 期：21
- 页码：8564-8572
- 全文大小：544K
- ISSN：1520-4804
文摘
New 1,1鈥?biphenylsulfonamides were synthesized and evaluated as inhibitors of the ubiquitous human carbonic anhydrase isoforms I, II, IX, XII, and XIV using acetazolamide (AAZ) as reference compound. The sulfonamides 1鈥?b>21 inhibited all the isoforms, with Ki values in the nanomolar range of concentration, and were superior to AAZ against all of them. X-ray crystallography and molecular modeling studies on the adducts that compound 20, the most potent hCA XIV inhibitor of the series (Ki = 0.26 nM), formed with the five hCAs, provided insight into the molecular determinants responsible for the high affinity of this molecule toward the target enzymes. The results pave the way to the development of 1.1鈥?biphenylsulfonamides as a new class of highy potent hCA XIV inhibitors.