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- Title
Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases.
- Authors
Ali, Majid; Bozdag, Murat; Farooq, Umar; Angeli, Andrea; Carta, Fabrizio; Berto, Paola; Zanotti, Giuseppe; Supuran, Claudiu T.
- 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.
- Subjects
CARBONIC anhydrase inhibitors; BENZENESULFONAMIDES; X-rays; INVESTIGATIONS; DRUG design; SULFONAMIDES
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 7, p2560
- ISSN
1661-6596
- Publication type
Academic Journal
- DOI
10.3390/ijms21072560