Applied Medical Informatics 2009;25(3-4):65-74.
Molecular Descriptors Family on Vertex Cutting: Relationships between Acelazolamide Structures and their Inhibitory Activity
Sorana D. BOLBOACĂ1,*, Monica M. MARTA1, Carmen E. STOENOIU2, Lorentz JÄNTSCHI2
1 “Iuliu Haţuieganu” University of Medicine and Pharmacy Cluj-Napoca, 13 Emil Isac, 400023 Cluj-Napoca, Romania.
2 Technical University of Cluj-Napoca, 15 C-tin Daicoviciu, 400020 Cluj-Napoca, Romania.
E-mail(s): sbolboaca@umfcluj.ro; mmarta@umfcluj.ro; carmen@j.academicdirect.org; lori@academicdirect.org
Abstract
Aim: To investigate the relationship between the structural information of acetazolamides and their inhibitory activity on carbonic anhydrase II. Material and Method: A sample of previously reported acetazolamides was studied. A pool of descriptors was calculated based on matrix representation and vertex cut in order to be included in the multiple linear regression analysis. The best performing model in terms of goodness-of-fit was analysed in order to assess its validity and reliability. The model was compared with previously reported models using a series of information and prediction criteria besides the Steiger’s Z test. Results: A model with a 99.77% determination coefficient proved to be the best performing model. The obtained model proved to have a less than 5% average of the absolute difference between the observed and the estimated inhibitory activity. The information and prediction criteria showed that the obtained model was better than the previously reported models. This conclusion is also sustained by the results of Steiger’s Z test (7.78; p = 3.66·10-15). Conclusion: The inhibitory activity on carbonic anhydrase II of acetazolamides proved to be of geometric and topologic nature and depended on the compounds’ melting point, relative atomic mass and atomic electronegativity.
Keywords: Sulfonamides; Carbonic Anhydrase II Inhibitors; quantitative Structure-Activity Relationships (qSAR); Molecular Descriptors Family on Vertex (MDFV).