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

International Journal of Molecular Sciences

Erol Eroğlu²  Hasan Türkmen¹  Semra Güler²  Selami Palaz² 

[1] Department of Chemistry, Faculty of Sciences and Arts, Harran University, Osmanbey Campus, 63300, Sanlıurfa, Turkey;Department of Physics, Faculty of Sciences and Arts, Harran University, Osmanbey Campus, 63300, Sanlıurfa, Turkey

关键词: Sulfonamides;    carbonic anhydrase (CA-II) inhibitors;    QSAR;    DFT;   

DOI  :  10.3390/i8020145

来源: mdpi

【 摘 要 】

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 R² values of ca. 0.94 and the squared cross-validated correlation coefficient R²_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.

【 授权许可】

Unknown   
© 2007 by MDPI