title: Arylamino bisphosphonates: potent and selective inhibitors of the tumor-associated carbonic anhydrase XII.
abstract: A set of matrix metalloproteinases (MMPs) inhibitors, containing a bisphosphonate moiety (BP), has been evaluated for the inhibitory activity of carbonic anhydrases (CAs, EC 4.2.1.1). Human (h) isoforms hCA I, II, IX, XII and XIV were included in the study due to their involvement in crucial physiologic and pathologic processes. Some of these molecules selectively inhibited CA XII in the nanomolar range, showing an attractive dual mechanism (anti-MMP and anti-CA) of action as potential antitumor agents. The BP inhibitors investigated in this study are also excellent leads for obtaining even more effective compounds able to selectively target membrane-bound CA XII and having the potential to be used as tools for understanding physiologic processes regulated by this isoform.
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi 'Aldo Moro' di Bari, Via Orabona 4, 70126 Bari, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Tauro
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi 'Aldo Moro' di Bari, Via Orabona 4, 70126 Bari, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Loiodice
authors.affiliation: Università degli Studi di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.affiliation: Università degli Studi di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy; Università degli Studi di Firenze, Polo Scientifico, Dipartimento NEIROFABA, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.affiliation: Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi 'Aldo Moro' di Bari, Via Orabona 4, 70126 Bari, Italy. Electronic address: paolo.tortorella@uniba.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tortorella
mesh_terms: D000086:Acetazolamide / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry*; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D020033:Protein Isoforms / Q000737:chemistry; D013329:Structure-Activity Relationship; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D004164:Diphosphonates; D007093:Imidazoles; D020033:Protein Isoforms; D000077211:Zoledronic Acid; D002256:Carbonic Anhydrases; C477378:carbonic anhydrase XII; D000086:Acetazolamide
keywords: Antitumor agent; Bisphosphonate; Carbonic anhydrase; Isoform-selective inhibitor; Matrix metalloproteinase inhibitor