Rev Electron Biomed / Electron J Biomed 2006;2:22-33. Jantschi et al. INHIBITORY ACTIVITY ON CARBONIC ANHYDRASE IV...

Purpose: To analyze the relationships between inhibitory activities on carbonic anhydrase IV and structures of substituted 1,3,4thiadiazole and 1,3,4-thiadiazoline disulfonamide through integration of compounds complex structure information by the use of Molecular Descriptors Family. Method: A number of forty compounds were used to generate and compute the molecular descriptors family and to build structureactivity relationships models. The obtained multi-varied models (the models with two, respectively with four descriptors) were validated by computing the cross-validation leave-one-out score (r2cv-loo), and analyzed through assessment of the squared correlation coefficients (r2), and the models stability (r2 r2cv-loo). The estimation abilities of the multi-varied MDF-SAR model with four descriptors were analyzed in training and test sets. Results: Analysis of the obtained models shows that the best results was obtained by the multi-varied model with four molecular descriptors (r2 = 0.920). The prediction abilities of this model is sustained by the cross validation leave-one-out score (r2cv-loo = 0.903), the model stability (r2 r2cv-loo = 0.017), and the results on training versus test analysis (no significant differences between correlation coefficients in training and test sets, p > 0.05). The multi-varied model which used four descriptors proved to render higher value of correlation coefficient comparing with previous reported models (p < 0.01). Conclusion: The multi-varied model with four descriptors is a solid and reliable one and indicates that the inhibition activity on carbonic anhydrase IV of substituted 1,3,4-thiadiazoleand 1,3,4-thiadiazoline-disulfonamides is like to be of geometry and topology nature, being in relation with compounds partial charges.