Pharmacology Research Today is a free monthly online journal that collates and summarizes the latest research about Pharmacology, including details on pharmacogenomics, drug development, new medications.

QSAR studies for the inhibition of the transmembrane isozymes XII and XIV of human carbonic anhydrase with a series of sulfonamides.

Tarko L, Supuran CT

Center of Organic Chemistry, Romanian Academy, Bucharest, Sector 6, Spl Independenţei 202B, MC 060023, Bucharest, Romania.

A diverse series of aromatic/heterocyclic sulfonamides possessing inhibitory action against the human transmembrane isoforms XII (cancer-associated) and XIV of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) has been used to develop QSAR models. Including all the 55 investigated sulfonamides in the calibration set, the predictive qualities of the QSAR equations were weak (r(2)=0.1771, F=5.70) for CA XII and good for CA XIV inhibition (r(2)=0.8222, F=57.04 before eliminating the outliers, and r(2)=0.8911, F=67.07 after eliminating them). The obtained models suggest a slightly different inhibition mechanism for the two isoforms. 3-Halogeno-4-amino-benzenesulfonamides were outliers for scaffold hopping for the inhibition of CA XIV. CA XIV inhibitory activity was proportional to the degree of molecular surface rugosity. For compounds of the type X-Ar-SO(2)NH(2) and Ar'-Ar-SO(2)NH(2) type, best inhibitors were detected when Ar/Ar' incorporates a heterocyclic moiety. These studies may be helpful for the design of more specific CA XII/XIV inhibitors, since this is the first QSAR model investigating them.

Published 16 July 2007 in Bioorg Med Chem, 15(17): 5666-71.
Full-text of this article is available online (may require subscription).

© 2005-2008 Pharmacology Research Today. All Rights Reserved.