Fibrate-based N-acylsulphonamides Targeting Carbonic Anhydrases: Synthesis, Biochemical Evaluation, and Docking Studies

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2019 May 11

PMID 31074307

Citations 5

Authors

Alessandra Ammazzalorso

Simone Carradori

Andrea Angeli

Atilla Akdemir

Barbara De Filippis

Marialuigia Fantacuzzi

Letizia Giampietro

Cristina Maccallini

Rosa Amoroso

Claudiu T Supuran

Affiliations

Soon will be listed here.

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.

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