Format

Send to

Choose Destination
Bioorg Med Chem Lett. 2014 Apr 15;24(8):1941-3. doi: 10.1016/j.bmcl.2014.03.001. Epub 2014 Mar 12.

Arylamino bisphosphonates: potent and selective inhibitors of the tumor-associated carbonic anhydrase XII.

Author information

1
Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi 'Aldo Moro' di Bari, Via Orabona 4, 70126 Bari, Italy.
2
Università degli Studi di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
3
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.
4
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.

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.

KEYWORDS:

Antitumor agent; Bisphosphonate; Carbonic anhydrase; Isoform-selective inhibitor; Matrix metalloproteinase inhibitor

PMID:
24650641
DOI:
10.1016/j.bmcl.2014.03.001
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center