Benzylaminoethyureido-tailed benzenesulfonamides: design, synthesis, kinetic and X-ray investigations on human carbonic anhydrases

DOI: 10.3390/ijms21072560

Authors: Majid Ali (Università degli Studi di Firenze; Università di Padova; COMSATS University Islamabad) , Murat Bozdag (Università degli Studi di Firenze) , Umar Farooq (COMSATS University Islamabad) , Andrea Angeli (Università degli Studi di Firenze) , Fabrizio Carta (Università degli Studi di Firenze) , Paola Berto (Università di Padova) , Giuseppe Zanotti (Università di Padova) , Claudiu T. Supuran (Università degli Studi di Firenze)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: International Journal Of Molecular Sciences , VOL 21

State: Published (Approved)
Published: April 2020
Diamond Proposal Number(s): 21741

Abstract: A drug design strategy of carbonic anhydrase inhibitors (CAIs) belonging to sulfonamides incorporating ureidoethylaminobenzyl tails is presented. A variety of substitution patterns on the ring and the tails, located on para- or meta- positions with respect to the sulfonamide warheads were incorporated in the new compounds. Inhibition of human carbonic anhydrases (hCA) isoforms I, II, IX and XII, involving various pathologies, was assessed with the new compounds. Selective inhibitory profile towards hCA II was observed, the most active compounds being low nM inhibitors (KIs of 2.8–9.2 nM, respectively). Extensive X-ray crystallographic analysis of several sulfonamides in an adduct with hCA I allowed an in-depth understanding of their binding mode and to lay a detailed structure-activity relationship.

Journal Keywords: carbonic anhydrase: sulfonamide; tail approach; X-ray crystallography

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I03-Macromolecular Crystallography

Added On: 30/04/2020 11:13

Documents:
ijms-21-02560.pdf

Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Structural biology Organic Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)