1. 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.
- Author
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Moi D, Nocentini A, Deplano A, Osman SM, AlOthman ZA, Piras V, Balboni G, Supuran CT, and Onnis V
- Subjects
- Antigens, Neoplasm metabolism, Carbonic Anhydrase II antagonists & inhibitors, Carbonic Anhydrase II metabolism, Carbonic Anhydrase IX antagonists & inhibitors, Carbonic Anhydrase IX metabolism, Carbonic Anhydrase Inhibitors chemical synthesis, Carbonic Anhydrase Inhibitors chemistry, Carbonic Anhydrases metabolism, Dose-Response Relationship, Drug, Humans, Hydrazines chemistry, Molecular Structure, Piperidines chemistry, Structure-Activity Relationship, Sulfonamides chemistry, Benzenesulfonamides, Carbonic Anhydrase Inhibitors pharmacology, Hydrazines pharmacology, Molecular Docking Simulation, Piperidines pharmacology, Sulfonamides pharmacology
- 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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