Hansch Analysis of Novel Acetamide Derivatives as Highly Potent and Specific MAO-A Inhibitors

Title:Hansch Analysis of Novel Acetamide Derivatives as Highly Potent and Specific MAO-A Inhibitors

Volume: 16 Issue: 2

Author(s): Ashish Pathak, Pradeep K. Singour, Amit K. Srivastava, Panchanan Gouda, Sunil Kumar and Bhupendra K. Goutam

Affiliation:

Keywords: QSAR, Mono Amino Oxidase, Acetamide derivatives, MAO-A inhibitors.

Abstract: 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 equations.

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 inhibitors.

Cite this article as:

Pathak Ashish, K. Singour Pradeep, K. Srivastava Amit, Gouda Panchanan, Kumar Sunil and K. Goutam Bhupendra, Hansch Analysis of Novel Acetamide Derivatives as Highly Potent and Specific MAO-A Inhibitors, Central Nervous System Agents in Medicinal Chemistry 2016; 16 (2) . https://dx.doi.org/10.2174/1871524916666151210143347