Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors

Rosaria Gitto; Francesca Maria Damiano; Laura De Luca; Stefania Ferro; Daniela Vullo; Claudiu T Supuran; Alba Chimirri

doi:10.1016/j.bmc.2011.10.015

Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors

Bioorg Med Chem. 2011 Dec 1;19(23):7003-7. doi: 10.1016/j.bmc.2011.10.015. Epub 2011 Oct 12.

Authors

Rosaria Gitto¹, Francesca Maria Damiano, Laura De Luca, Stefania Ferro, Daniela Vullo, Claudiu T Supuran, Alba Chimirri

Affiliation

¹ Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, I-98168 Messina, Italy.

PMID: 22041171
DOI: 10.1016/j.bmc.2011.10.015

Abstract

In a previous paper we identified several 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-sulfonamides that displayed inhibitory effects toward selected carbonic anhydrase isozymes at micromolar concentration. In order to deepen the structure-activity relationships (SARs) and identify novel compounds with improved activity, we synthesized a series of monomethoxy analogues of the previously investigated dimethoxy derivatives. The evaluation of biological profile has been focused on in vitro effects against several CA isoforms. The new monomethoxy derivatives showed higher hCA inhibitory effects against several isoforms compared to the dimethoxy analogues. Particularly, some of these compounds (e.g., 1b and 1h) showed low nanomolar K(I) values and excellent selectivity for hCA IX and hCA XIV versus hCA I and II inhibition.

Publication types

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

MeSH terms

Carbonic Anhydrase Inhibitors / chemical synthesis*
Carbonic Anhydrase Inhibitors / pharmacology*
Humans
Structure-Activity Relationship
Tetrahydroisoquinolines / chemical synthesis*
Tetrahydroisoquinolines / pharmacology*

Substances

Carbonic Anhydrase Inhibitors
Tetrahydroisoquinolines