Mohamed Menshawy A, Abdel-Aziz Alaa A-M, Sakr Helmy M, El-Azab Adel S, Bua Silvia, Supuran Claudiu T
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia; Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Bioorg Med Chem. 2017 Apr 15;25(8):2524-2529. doi: 10.1016/j.bmc.2017.03.017. Epub 2017 Mar 9.
A series of sulfonamides was obtained by reacting substituted-2-(1,3-dioxo-1,3-dihydroisobenzofuran-5-carboxamido)benzoic acids with aromatic sulfonamides incorporating primary amino moieties. The new compounds were investigated as inhibitor of four carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I and II, and the α- and β-class CAs from the pathogenic bacterium Vibrio cholerae, VchCAα and VhcCAβ. hCA I was effectively inhibited by the new sulfonamides, with inhibition constants in the range of 4.9-96.0nM. hCA II also showed high affinity for these compounds (Ks of 2.1-22.3nM), whereas the two bacterial enzymes were less effectively inhibited, with Ks of 281-3192nM for VchCAα, and 5.40-9.26µM for VhcCAβ. As the physiological function hCA I is poorly understood, and it was recently shown to be involved in the pathogenesis of cerebral malaria and amyotrophic lateral sclerosis, selective and effective inhibitors may be useful as tools or drugs for better understanding this abundant isoform.
通过使取代的2-(1,3-二氧代-1,3-二氢异苯并呋喃-5-甲酰胺基)苯甲酸与含有伯氨基部分的芳族磺酰胺反应，得到了一系列磺酰胺。研究了这些新化合物作为四种碳酸酐酶（CA，EC 4.2.1.1）同工型的抑制剂，即人（h）hCA I和II，以及来自病原菌霍乱弧菌的α-和β-类CA，VchCAα和VhcCAβ。新的磺酰胺对hCA I有有效抑制作用，抑制常数在4.9-96.0 nM范围内。hCA II对这些化合物也表现出高亲和力（Ks为2.1-22.3 nM），而两种细菌酶受到的抑制作用较弱，VchCAα的Ks为281-3192 nM，VhcCAβ的Ks为5.40-9.26 μM。由于对hCA I的生理功能了解甚少，并且最近发现它与脑型疟疾和肌萎缩侧索硬化症的发病机制有关，选择性和有效的抑制剂可能作为工具或药物有助于更好地了解这种丰富的同工型。
