Hansch Analysis of Novel Acetamide Derivatives as Highly Potent and Specific MAO-A Inhibitors
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Central nervous system agents in medicinal chemistry - 16(2016), 2 vom: 04., Seite 143-51 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pathak, Ashish [VerfasserIn] |
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| Themen: |
8XOE1JSO29 |
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| Anmerkungen: |
Date Completed 23.02.2017 Date Revised 13.11.2019 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM255441029 |
|---|
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| 245 | 1 | 0 | |a Hansch Analysis of Novel Acetamide Derivatives as Highly Potent and Specific MAO-A Inhibitors |
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| 500 | |a Date Completed 23.02.2017 | ||
| 500 | |a Date Revised 13.11.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: This study may be useful in the designing of more potent substituted acetamide derivatives as specific MAOA inhibitors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Acetamides |2 NLM | |
| 650 | 7 | |a Monoamine Oxidase Inhibitors |2 NLM | |
| 650 | 7 | |a acetamide |2 NLM | |
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| 650 | 7 | |a Monoamine Oxidase |2 NLM | |
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| 700 | 1 | |a Srivastava, Amit K |e verfasserin |4 aut | |
| 700 | 1 | |a Gouda, Panchanan |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Sunil |e verfasserin |4 aut | |
| 700 | 1 | |a Goutam, Bhupendra K |e verfasserin |4 aut | |
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