Background: A quantitative structure-activity relationship (QSAR) study of novel
Acetamide derivatives as specific Mono amino oxidase (MAO) A inhibitory agents was performed
with 28 compounds to derive QSAR models for better activity and lesser side effects.
Methods: Various thermodynamic, electronic and steric parameters were calculated using Chem 3D package of molecular
modeling software Chemoffice 7.0. QSAR models were generated employing sequential multiple regression method using
in–house statistical program VALSTAT. The best models were selected from the various statistically significant
Results: The study revealed that an increase in the bulkiness of the substituent’s and molecular solvent accessible surface
area is beneficial to the biological activity and the substitution of two interacting groups should be separated by more than
three atoms will give better biological activity. Model also suggests that the presence of the comparatively less lipophilic
group may increase MAO-A inhibitory activity and substituent that decrease the flexibility and increase rigidity of the nucleus
will enhance the activity. The best QSAR model was selected, having a correlation coefficient (r) = 0.93271, coefficient
of determination (r2) = 0.8509 with a standard deviation of predictivity (SDEP) = 0.31287 and cross validated
squared correlation coefficient (Q2) = 0.92. The predictive ability of the selected model was also confirmed by leave one
out cross validation and r2 predicted (r2 pred) was 0.764.
Conclusion: This study may be useful in the designing of more potent substituted acetamide derivatives as specific MAOA