In vivo targeting of tumor-associated carbonic anhydrases using acetazolamide derivatives

Julia K J Ahlskog; Christoph E Dumelin; Sabrina Trüssel; Jessica Mårlind; Dario Neri

doi:10.1016/j.bmcl.2009.06.022

In vivo targeting of tumor-associated carbonic anhydrases using acetazolamide derivatives

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4851-6. doi: 10.1016/j.bmcl.2009.06.022. Epub 2009 Jun 13.

Authors

Julia K J Ahlskog¹, Christoph E Dumelin, Sabrina Trüssel, Jessica Mårlind, Dario Neri

Affiliation

¹ Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, CH-8093 Zurich, Switzerland.

PMID: 19615903
DOI: 10.1016/j.bmcl.2009.06.022

Abstract

We describe the synthesis and characterization of two acetazolamide derivatives containing either a charged fluorophore or an albumin-binding moiety, which restrict binding to carbonic anhydrase IX and XII present on tumor cells. In vivo studies showed the preferentially targeting of tumor cells by the fluorescent acetazolamide derivative and the ability of the albumin-binding acetazolamide derivative to cause tumor retardation in a SK-RC-52 xenograft model of cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetamides / chemistry
Acetamides / pharmacology*
Animals
Antigens, Neoplasm / chemistry
Antigens, Neoplasm / metabolism*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Carbonic Anhydrase IX
Carbonic Anhydrase Inhibitors / chemistry
Carbonic Anhydrase Inhibitors / pharmacology*
Carbonic Anhydrases / chemistry
Carbonic Anhydrases / metabolism*
Cell Line, Tumor
Colorectal Neoplasms / drug therapy
Colorectal Neoplasms / enzymology
Fluorescent Dyes / chemistry
Humans
Mice
Mice, Nude
Xenograft Model Antitumor Assays

Substances

Acetamides
Antigens, Neoplasm
Antineoplastic Agents
Carbonic Anhydrase Inhibitors
Fluorescent Dyes
CA9 protein, human
Carbonic Anhydrase IX
Carbonic Anhydrases
carbonic anhydrase XII