化学
碳酸酐酶
跨膜蛋白
基因亚型
胞浆
部分
酶
生物化学
立体化学
受体
基因
作者
Fabio Pacchiano,Fabrizio Carta,Paul C. McDonald,Yuanmei Lou,Daniela Vullo,Andrea Scozzafava,Shoukat Dedhar,Claudiu T. Supuran
摘要
A series of ureido-substituted benzenesulfonamides was prepared that showed a very interesting profile for the inhibition of several human carbonic anhydrases (hCAs, EC 4.2.1.1), such as hCAs I and II (cytosolic isoforms) and hCAs IX and XII (transmembrane, tumor-associated enzymes). Excellent inhibition of all these isoforms has been observed with various members of the series, depending on the substitution pattern of the urea moiety. Several low nanomolar CA IX/XII inhibitors also showing good selectivity for the transmembrane over the cytosolic isoforms have been discovered. One of them, 4-{[(3'-nitrophenyl)carbamoyl]amino}benzenesulfonamide, significantly inhibited the formation of metastases by the highly aggressive 4T1 mammary tumor cells at pharmacologic concentrations of 45 mg/kg, constituting an interesting candidate for the development of conceptually novel antimetastatic drugs.
科研通智能强力驱动
Strongly Powered by AbleSci AI