Some QSAR Studies for a Group of Sulfonamide Schiff Base as Carbonic Anhydrase CA II Inhibitors

Erol Eroglu

doi:10.3390/ijms9020181

Abstract

In the present study, quantitative structure-activity-relationship (QSAR) study on a group of sulfonamide Schiff-base inhibitors of Carbonic Anhydrase (CA) enzyme has been carried out using Codessa Pro methodology and software. Linear regression QSAR models of the biological activity (Ki) of 38 inhibitors of carbonic anhydrase CA-II isozyme were established with 12 different molecular descriptors which were selected from more than hundreds of geometrical, topological, quantum-mechanical, and electronic types of descriptors and calculated using Codessa Pro software. Among the models presented in this study, statistically the most significant one is a five-parameter equation with correlation coefficient, R(2) values of ca. 0.840, and the cross-validated correlation coefficient, R(2) values of ca. 0.777. The obtained models allowed us to reveal some physicochemical and structural factors, which are strongly correlated with the biological activity of the compounds.

Highlights

The metallo-protein carbonic anhydrase (CA, EC 4.2.1.1) is one of the most widely spread biological catalysts all over the phylogenetic tree
To the best of our knowledge, four quantitative structure–activity-relationship (QSAR) studies [26,27,28, 10] have been carried out using sulfonamides with Schiff base as Carbonic anhydrase inhibitors
We investigated QSAR for 38 sulfanilamide Schiff’s base inhibitors of the physiologically relevant isozyme CAII using Codessa Pro approach [29]

Summary

Introduction

The metallo-protein carbonic anhydrase (CA, EC 4.2.1.1) is one of the most widely spread biological catalysts all over the phylogenetic tree. Isozymes I, II, and IV are involved in respiration and regulation of the acid/base homeostasis. CA II is involved in the bone development and in functions such as the differentiation of osteoclasts or the provision of acid for bone resorption in osteoclasts [1,2,3,4] The presence of these isozymes in so many tissues and in a number of different isoforms represents an attractive objective for the design of inhibitors with biomedical applications. To the best of our knowledge, four QSAR studies [26,27,28, 10] have been carried out using sulfonamides with Schiff base as Carbonic anhydrase inhibitors. The results of this study may help estimate the inhibition activity of sulfonamide with Schiff base of this series, prior to synthesis

Computational details

Results

Discussion

H 2 OH

Conclusion

Experimental Section