邻苯二甲酰亚胺封端的苯磺酰胺衍生物的碳酸酐酶抑制活性。

Carbonic anhydrase inhibitory activity of phthalimide-capped benzene sulphonamide derivatives.

机构信息

Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Ranchi, India.

Department of Pharmaceutical Chemistry, Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, India.

出版信息

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2235089. doi: 10.1080/14756366.2023.2235089.

A series of phthalimide-capped benzene sulphonamides (-) reported by our group for dengue protease inhibitory activity have been evaluated for their carbonic anhydrase (hCA, EC 4.2.1.1) inhibitory activity against hCA I, hCA II. Compounds , , , and showed hCA I inhibition, whereas , , and showed hCA II inhibition at nanomolar concentrations. Among these compounds, displayed potent inhibitory activity against the hCA I (Ki = 28.5 nM) and hCA II (Ki = 2.2 nM), being 10 and 6 times more potent than acetazolamide, a standard inhibitor (Ki = 250 nM and 12 nM), respectively. Furthermore, this compound displayed 14-fold selectivity towards the hCA II isoform compared to hCA I. Molecular docking and MD simulations were performed to understand the atomic level interactions responsible for the selectivity of compound towards hCA II.

我们小组曾报道过一系列以邻苯二甲酰亚胺封端的苯磺酰胺类化合物（-），具有抗登革热蛋白酶活性，现对其碳酸酐酶（hCA，EC 4.2.1.1）抑制活性进行评估，包括 hCA I 和 hCA II。化合物、、、对 hCA I 具有抑制作用，而、、则在纳摩尔浓度下对 hCA II 具有抑制作用。在这些化合物中，化合物对 hCA I（Ki = 28.5 nM）和 hCA II（Ki = 2.2 nM）表现出很强的抑制活性，分别比标准抑制剂乙酰唑胺（Ki = 250 nM 和 12 nM）强 10 倍和 6 倍。此外，与 hCA I 相比，该化合物对 hCA II 同工酶的选择性高 14 倍。通过分子对接和 MD 模拟，研究了化合物对 hCA II 选择性的原子水平相互作用。