Fibrate-based N-acylsulphonamides targeting carbonic anhydrases: synthesis, biochemical evaluation, and docking studies. (1st January 2019)

• Record Type: Journal Article
• Authors: Ammazzalorso, Alessandra; Carradori, Simone; Angeli, Andrea; Akdemir, Atilla; De Filippis, Barbara; Fantacuzzi, Marialuigia; Giampietro, Letizia; Maccallini, Cristina; Amoroso, Rosa; Supuran, Claudiu T.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 34:Number 1(2019)
• Page Start: 1051
• Page End: 1061
• Publication Date: 2019-01-01
• Subjects: N-acylsulphonamides -- carbonic anhydrase -- PPAR antagonist -- fibrate derivatives -- benzothiazole -- benzophenone; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2019.1611801
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: A large library of fibrate-based N -acylsulphonamides was designed, synthesised, and fully characterised in order to propose them as zinc binders for the inhibition of human carbonic anhydrase (hCA) enzymatic activity. Synthesised compounds were tested against four hCAs (I, II, IX, and XII) revealing a promising submicromolar inhibitory activity characterised by an isozyme selectivity pattern. Structural modifications explored within this scaffold are: presence of an aryl ring on the sulphonamide, p -substitution of this aryl ring, benzothiazole or benzophenone as core nuclei, and an n -propyl chain or a geminal dimethyl at Cα carbon. Biological results fitted well with molecular modelling analyses, revealing a putative direct interaction with the zinc ion in the active site of hCA I, II and IX. These findings supported the exploration of less investigated secondary sulphonamides as potential hCA inhibitors.