3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors
Acetyl-CoA carboxylase (ACC) is a crucial metabolic enzyme, which plays a vital role in fatty acid metabolism and obesity induced type 2 diabetes. Herein, we have performed 3D-QSAR and molecular docking analysis on a novel series of (4-piperidinyl)-piperazines to design potent ACC inhibitors. This s...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-02-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535212002559 |
| _version_ | 1818923911812743168 |
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| author | Udghosh Singh Rahul Prakashchand Gangwal Gaurao V. Dhoke Rameshwar Prajapati Mangesh Damre Abhay T. Sangamwar |
| author_facet | Udghosh Singh Rahul Prakashchand Gangwal Gaurao V. Dhoke Rameshwar Prajapati Mangesh Damre Abhay T. Sangamwar |
| author_sort | Udghosh Singh |
| collection | DOAJ |
| description | Acetyl-CoA carboxylase (ACC) is a crucial metabolic enzyme, which plays a vital role in fatty acid metabolism and obesity induced type 2 diabetes. Herein, we have performed 3D-QSAR and molecular docking analysis on a novel series of (4-piperidinyl)-piperazines to design potent ACC inhibitors. This study correlates the ACC inhibitory activities of 68 (4-piperidinyl)-piperazine derivatives with several stereo-chemical parameters representing steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields. The CoMFA and CoMSIA models exhibited excellent rncv2 values of 0.974 and 0.985, and rcv2 values of 0.671 and 0.693, respectively. CoMFA predicted rpred2 of 0.910 and CoMSIA predicted rpred2 of 0.963 showed that the predicted values were in good agreement with experimental values. Glide5.5 program was used to explore the binding mode of inhibitors inside the active site of ACC. We have accordingly designed novel ACC inhibitors by utilising the LeapFrog and predicted with excellent inhibitory activity in the developed models. |
| first_indexed | 2024-12-20T02:16:58Z |
| format | Article |
| id | doaj.art-13eeb128bcc44023b2f671ed5ce41560 |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-12-20T02:16:58Z |
| publishDate | 2017-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-13eeb128bcc44023b2f671ed5ce415602022-12-21T19:56:54ZengElsevierArabian Journal of Chemistry1878-53522017-02-0110S1S617S62610.1016/j.arabjc.2012.10.0233D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitorsUdghosh SinghRahul Prakashchand GangwalGaurao V. DhokeRameshwar PrajapatiMangesh DamreAbhay T. SangamwarAcetyl-CoA carboxylase (ACC) is a crucial metabolic enzyme, which plays a vital role in fatty acid metabolism and obesity induced type 2 diabetes. Herein, we have performed 3D-QSAR and molecular docking analysis on a novel series of (4-piperidinyl)-piperazines to design potent ACC inhibitors. This study correlates the ACC inhibitory activities of 68 (4-piperidinyl)-piperazine derivatives with several stereo-chemical parameters representing steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields. The CoMFA and CoMSIA models exhibited excellent rncv2 values of 0.974 and 0.985, and rcv2 values of 0.671 and 0.693, respectively. CoMFA predicted rpred2 of 0.910 and CoMSIA predicted rpred2 of 0.963 showed that the predicted values were in good agreement with experimental values. Glide5.5 program was used to explore the binding mode of inhibitors inside the active site of ACC. We have accordingly designed novel ACC inhibitors by utilising the LeapFrog and predicted with excellent inhibitory activity in the developed models.http://www.sciencedirect.com/science/article/pii/S1878535212002559Acetyl-CoA carboxylases(4-Piperidinyl)-piperazinesCoMFACoMSIAMolecular dockingLeapFrog |
| spellingShingle | Udghosh Singh Rahul Prakashchand Gangwal Gaurao V. Dhoke Rameshwar Prajapati Mangesh Damre Abhay T. Sangamwar 3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors Arabian Journal of Chemistry Acetyl-CoA carboxylases (4-Piperidinyl)-piperazines CoMFA CoMSIA Molecular docking LeapFrog |
| title | 3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors |
| title_full | 3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors |
| title_fullStr | 3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors |
| title_full_unstemmed | 3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors |
| title_short | 3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors |
| title_sort | 3d qsar and molecular docking analysis of 4 piperidinyl piperazines as acetyl coa carboxylases inhibitors |
| topic | Acetyl-CoA carboxylases (4-Piperidinyl)-piperazines CoMFA CoMSIA Molecular docking LeapFrog |
| url | http://www.sciencedirect.com/science/article/pii/S1878535212002559 |
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