Bis-benzoxaboroles: Design, Synthesis, and Biological Evaluation as Carbonic Anhydrase Inhibitors

Abstract : 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.
Type de document :
Article dans une revue
Domaine :
Liste complète des métadonnées
Contributeur : Philippe Falque <>
Soumis le : mercredi 4 septembre 2019 - 16:58:23
Dernière modification le : jeudi 5 septembre 2019 - 01:21:53




Adèle Larcher, Alessio Nocentini, Claudiu Supuran, Jean-Yves Winum, Arie van der Lee, et al.. Bis-benzoxaboroles: Design, Synthesis, and Biological Evaluation as Carbonic Anhydrase Inhibitors. ACS Medicinal Chemistry Letters, American Chemical Society, 2019, 10 (8), pp.1205-1210. ⟨10.1021/acsmedchemlett.9b00252⟩. ⟨hal-02278875⟩



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