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Bioorg Med Chem Lett. 2014 Jun 15;24(12):2617-20. doi: 10.1016/j.bmcl.2014.04.077. Epub 2014 Apr 30.

Dual carbonic anhydrase/matrix metalloproteinase inhibitors incorporating bisphosphonic acid moieties targeting bone tumors.

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, Dipartimento di Chimica, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
3
Università degli Studi di Firenze, Dipartimento di Chimica, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy; Università degli Studi di Firenze, Neurofarba Dept., Section of Pharmaceutical and Nutriceutical Sciences, Via U. 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 bisphosphonate matrix metalloproteinase (MMP) inhibitors was investigated for inhibitory activity against several carbonic anhydrase (CA, EC 4.2.1.1) isozymes, some of which are overexpressed in hypoxic tumors. Some of the bisphosphonate revealed to be very potent inhibitors (in the low nanomolar range) of the cytosolic isoform CA II and the membrane-bound CA IX, XII and XIV isozymes, a feature useful for considering them as interesting compounds for bone resorption inhibition applications. We suggest here that it is possible to develop dual enzyme inhibitors bearing bisphosphonate moieties that may target both MMPs and CAs, two families of enzymes involved in tumor formation, growth, and metastasis.

KEYWORDS:

Bisphosphonate; Bone resorption inhibitor; Carbonic anhydrase; Enzyme inhibitor; Matrix metalloproteinase inhibitor

PMID:
24813742
DOI:
10.1016/j.bmcl.2014.04.077
[Indexed for MEDLINE]

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