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Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases.

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.

SUBMITTER: Ali M

PROVIDER: S-EPMC7177897 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases.

Ali Majid M Bozdag Murat M Farooq Umar U Angeli Andrea A Carta Fabrizio F Berto Paola P Zanotti Giuseppe G Supuran Claudiu T CT

International journal of molecular sciences 20200407 7

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 inhibitor ...[more]

PMID: 32272689

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