A DFT-Based QSARs Study of Acetazolamide/Sulfanilamide Derivatives with Carbonic Anhydrase (CA-II) Isozyme Inhibitory Activity

Abstract

This study presents Quantitative Structure Activity Relationships (QSAR) study on a pool of 18 bio-active sulfonamide compounds which includes five acetazolamide derivatives, eight sulfanilamide derivatives and five clinically used sulfonamides molecules as drugs namely acetazolamide, methazolamide, dichlorophenamide, ethoxolamide and dorzolamide. For all the compounds, initial geometry optimizations were carried out with a molecular mechanics (MM) method using the MM+ force fields. The lowest energy conformations of the compounds obtained by the MM method were further optimized by the Density Functional Theory (DFT) method by employing Becke's three-parameter hybrid functional (B3LYP) and 6-31G (d) basis set. Molecular descriptors, dipole moment, electronegativity, total energy at 0 K, entropy at 298 K, HOMO and LUMO energies obtained from DFT calculations provide valuable information and have a significant role in the assessment of carbonic anhydrase (CA-II) inhibitory activity of the compounds. By using the multiple linear regression technique several QSAR models have been drown up with the help these calculated descriptors and carbonic anhydrase (CA-II) inhibitory data of the molecules. Among the obtained QSAR models presented in the study, statistically the most significant one is a five parameters linear equation with the squared correlation coefficient R 2 values of ca. 0.94 and the squared cross-validated correlation coefficient R 2 CV values of ca. 0.85. The results were discussed in the light of the main factors that influence the inhibitory activity of the carbonic anhydrase (CA-II) isozyme.

QSAR analysis of 2-benzoxazolyl hydrazone derivatives for anticancer activity and its possible target prediction

“…It is a global molecular property that describes the electrophilicity of a compound and it measures the ability of a molecule to act as an electron acceptor. Lower LUMO values lead to stronger electrophilicity (Iglika et al, 2006;Balasubramanian et al, 2007;Erol et al, 2007). The positive contribution of this descriptor explains that an increase in the LUMO value lead to a decrease in the electrophilicity strength of the molecule, which is favorable for the activity.…”

Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein−Ligand Binding

“…In these studies, CA provides a model for proteins that fold and unfold through a molten-globule intermediate and for proteins that comprise mostly β-sheets and are prone to aggregate during refolding. [854][855][856][857][858][859][860][861][862][863][864][865] and activators 866 of various isozymes of CA. The interaction of CA with surfaces has also been investigated for delivering inhibitors to CA via nanoparticles 867 and for disrupting the self-assembly of ion channels.…”

In silico receptor-based drug design of X,Y-benzenesulfonamide derivatives as selective COX-2 inhibitors

“…On the other hand, the electronic character of sulfonamide derivatives and its correlation with its inhibitory activity over the acetylcholinesterase protein has been properly studied by using quantum chemical descriptors, such as HOMO, LUMO, dipole moment, etc. [31]; hence, they were included in the descriptor pool used in this study.…”