2. Academic Validation
  3. Appliance of the piperidinyl-hydrazidoureido linker to benzenesulfonamide compounds: Synthesis, in vitro and in silico evaluation of potent carbonic anhydrase II, IX and XII inhibitors

Appliance of the piperidinyl-hydrazidoureido linker to benzenesulfonamide compounds: Synthesis, in vitro and in silico evaluation of potent carbonic anhydrase II, IX and XII inhibitors

  • Bioorg Chem. 2020 May;98:103728. doi: 10.1016/j.bioorg.2020.103728.
Davide Moi 1,  Alessio Nocentini 2,  Alessandro Deplano 3,  Sameh M Osman 4,  Zeid A AlOthman 4,  Valentina Piras 1,  Gianfranco Balboni 1,  Claudiu T Supuran 5,  Valentina Onnis 6
Affiliations

Affiliations

  • 1 Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, University Campus, S.P. n° 8, Km 0.700, I-09042 Monserrato (CA), Italy.
  • 2 Department NEUROFARBA - Pharmaceutical and Nutraceutical Section, University of Firenze, via Ugo Schiff 6, I-50019 Sesto Fiorentino, Firenze, Italy.
  • 3 Pharmacelera, Placa Pau Vila, 1, Sector 1, Edificio Palau de Mar, Barcelona 08039, Spain.
  • 4 Chemistry Department, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.
  • 5 Department NEUROFARBA - Pharmaceutical and Nutraceutical Section, University of Firenze, via Ugo Schiff 6, I-50019 Sesto Fiorentino, Firenze, Italy. Electronic address: [email protected].
  • 6 Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, University Campus, S.P. n° 8, Km 0.700, I-09042 Monserrato (CA), Italy. Electronic address: [email protected].
PMID: 32182519 DOI: 10.1016/j.bioorg.2020.103728
Abstract

Herein we report on a new series of hydrazidoureidobenzensulfonamides investigated as inhibitors of the cytosolic human (h) hCA I and II isoforms, as well as the transmembrane, tumor-associated enzymes hCA IX and XII. The reported derivatives contain a 4-substituted piperidine fragment in which the hydrazidoureido linker has been involved as spacer between the benzenesulfonamide fragment which binds the zinc ion from the active site, and the tail of the inhibitor. Depending on the substitution pattern at the piperidine ring, low nanomolar inhibitors were detected against hCA II, hCA IX and hCA XII, making the new class of sulfonamides of interest for various pharmacologic applications.

Keywords

Antitumor; Inhibitor; Metalloenzyme; Selectivity; Sulfonamides.

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