QSAR studies for the inhibition of the transmembrane carbonic anhydrase isozyme XIV with sulfonamides using PRECLAV software

Abstract

QSAR studies for the inhibition of isozyme XIV of human carbonic anhydrase (CA, EC 4.2.1.1) by a series of sulfonamides including clinically used derivatives (acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and zonisamide) are presented. Statistical calculations done using the PRECLAV program, for the correlation between the observed inhibition values and the calculated ones were good (s = 0.2416, r² = 0.9259, F = 75.0196, ). The obtained results by using PRECLAV descriptors have been compared with those where the descriptors have been calculated with HYPERCHEM. The obtained QSAR equations pointed out the fact that the CA inhibitory activity decreased for unsubstituted (at the organic scaffold) aromatic/heteroaromatic sulfonamides, but was favored by the presence of alkyl groups substituting the scaffold, which led to a higher internal topological diversity, as well as by the presence of condensed aromatic rings in the structure of these enzyme inhibitors.

Keywords::

• QSAR
• Carbonic anhydrase XIV
• sulfonamides
• PRECLAV
• HyperChem
• NCSS
• inhibition

Acknowledgements

One of the authors (S. Singh) expresses her thanks to the Department of Science & Technology, Government of India, New Delhi, for awarding DST project SR / WOS-A / CS-61 / 2004 under Woman Scientists scheme, and to Dr. R.P.Singh, Principal, Bareilley College, Bareilley, India for his personal interest,encouragement and for providing facilities for carrying out the present study.The project was also in part financed by an EU grant to CTS and AS of the 6^th framework programme (DeZnIT project).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.