Bis-benzoxaboroles: Design, Synthesis, and Biological Evaluation as Carbonic Anhydrase Inhibitors
| Autor: | Michael Smietana, Jean-Jacques Vasseur, Danielle Laurencin, Adèle Larcher, Claudiu T. Supuran, Jean-Yves Winum, Arie van der Lee, Alessio Nocentini |
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| Přispěvatelé: | Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), NEUROFARBA Department [Firenze, Italy], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institut Européen des membranes (IEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Gene isoform
Benzoxaborole biology 010405 organic chemistry Chemistry Stereochemistry Organic Chemistry Imine carbonic anhydrase multivalency 01 natural sciences Biochemistry Transmembrane protein 0104 chemical sciences 010404 medicinal & biomolecular chemistry Cytosol chemistry.chemical_compound Carbonic anhydrase Reagent Amide Drug Discovery biology.protein [CHIM]Chemical Sciences enzyme inhibition Biological evaluation |
| Zdroj: | ACS Medicinal Chemistry Letters ACS Medicinal Chemistry Letters, American Chemical Society, 2019, 10 (8), pp.1205-1210. ⟨10.1021/acsmedchemlett.9b00252⟩ ACS Med Chem Lett |
| ISSN: | 1948-5875 |
| Popis: | International audience; The synthesis, characterization, and biological evaluation of a series of compounds incorporating two or three benzoxaborole moieties is reported. Three different synthetic strategies were used to explore within this series as much chemical space as possible, all starting from the 6-aminobenzoxaborole reagent: amide coupling, imine bond formation, and squarate coupling. Eleven new compounds were isolated in pure form, and single crystals were obtained for two of them. These compounds were then evaluated as carbonic anhydrase inhibitors against the cytosolic hCA I and II and the transmembrane hCA IV, IX, and XII isoforms. While the benzoxaborole scaffold has been recently introduced as a new chemotype for carbonic anhydrase inhibition, these new multivalent derivatives exhibited superior inhibitory activity against the tumor-associated isoform hCA IX. In particular, compared to monovalent 6-aminobenzoxaborole (K-I = 813 nM) and 6-carboxybenzoxaborole (K-I = 400 nM), derivative 2h characterized by a glutamic acid structural core and two benzoxaborole moieties was found to be more potent (K-I = 64 nM) and more selective over human hCA II. |
| Databáze: | OpenAIRE |
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