Synthesis and investigation of selective human carbonic anhydrase IX, XII inhibitors using coumarins bearing a sulfonamide or biotin moiety.

Autor: Begines P; NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, Florence, 50019, Italy; Department of Organic Chemistry, Faculty of Chemistry, University of Seville, Profesor García González 1, Seville, E-41012, Spain. Electronic address: pbegines@us.es., Bonardi A; NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, Florence, 50019, Italy; NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy., Giovannuzzi S; NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, Florence, 50019, Italy., Nocentini A; NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, Florence, 50019, Italy; NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy., Gratteri P; NEUROFARBA Department, Pharmaceutical and Nutraceutical Section, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Florence, Via U. Schiff 6, 50019, Sesto Fiorentino, Firenze, Italy., De Luca V; Department of Biology, Agriculture and Food Sciences, Institute of Biosciences and Bioresources, Napoli, Italy., González-Bakker A; BioLab, University Institute of Bio-Organic 'Antonio González', University of la Laguna, C/ Astrofísico Francisco Sánchez 2, 38206, La Laguna, Spain., Padrón JM; BioLab, University Institute of Bio-Organic 'Antonio González', University of la Laguna, C/ Astrofísico Francisco Sánchez 2, 38206, La Laguna, Spain., Capasso C; Department of Biology, Agriculture and Food Sciences, Institute of Biosciences and Bioresources, Napoli, Italy., Supuran CT; NEUROFARBA Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, University of Florence, Florence, 50019, Italy. Electronic address: claudiu.supuran@unifi.it.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2024 Dec 01; Vol. 404, pp. 111284. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1016/j.cbi.2024.111284
Abstrakt: The role of carbonic anhydrases isoforms (CAs) IX and XII in the pathogenesis and progression of many types of solid tumors is well known. In this context, selective CA inhibitors (CAIs) towards the mentioned isoforms is a validated strategy for the development of agents to target cancer. For this purpose, novel coumarin derivatives based on the hybridization with arylsulfonamide or biotin scaffolds were synthesized and tested as inhibitors of four different human carbonic anhydrases isoforms: hCA I, II, IX and XII. Coumarin-sulfonamide derived 27, with a thiourea moiety and triazole as linker, showed the highest inhibition activity against hCA XII with an inhibition constant (K I ) of 7.5 nM and afforded a very good selectivity over hCA I. Compound 32 was the most potent inhibitor against hCA IX (K I  = 6.3 nM), 4-fold stronger than the drug acetazolamide AAZ (K I  = 25 nM), used herein as a reference compound, and showed remarkable selectivity over hCA I and II. The coumarin-biotin derivatives 37-39 showed outstanding selectivity towards on-target enzymes (hCA IX and XII) and appear as plausible leads for designing of CAIs.
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 © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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