a Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome , Rome , Italy.
b Department of Pharmacy, "G. D'Annunzio", University of Chieti-Pescara , Chieti , Italy.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):1400-1413. doi: 10.1080/14756366.2019.1651315.
A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives.
合成并测试了基于 2-（苄基亚磺酰基）苯甲酸支架的大量衍生物，作为针对四种不同人碳酸酐酶（hCA I、II、IX 和 XII，EC 4.2.1.1）的非典型抑制剂。对主要官能团周围的化学空间进行了探索，从而在微摩尔/纳摩尔范围内发现了选择性的 hCA IX 抑制剂，从而在这个多功能支架内建立了稳健的构效关系。对一些选定的手性化合物进行了 HPLC 分离，并对相应的对映体进行了生物学评价，同时对最活跃的衍生物进行了分子建模研究。
