Pyrido-pyrimido-thiadiazinones: green synthesis, molecular docking studies and biological investigation as obesity inhibitors
Obesity is a global public health concern brought on by a combination of excessive dietary intake, inactivity and genetic predisposition. Pyridopyrimidines have received considerable interest in the development of obesity and diabetes. Mannich reaction was applied on 2-thioxo-pyridopyrimidinone deri...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Taibah University for Science |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/16583655.2022.2159210 |
| _version_ | 1797978363771486208 |
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| author | Ferid Yaccoubi Mohamed El-Naggar Fathy M. Abdelrazek Sobhi M. Gomha Mohamed S. Farghaly Tariq Z. Abolibda Lobna A. Ali Aboubakr H. Abdelmonsef |
| author_facet | Ferid Yaccoubi Mohamed El-Naggar Fathy M. Abdelrazek Sobhi M. Gomha Mohamed S. Farghaly Tariq Z. Abolibda Lobna A. Ali Aboubakr H. Abdelmonsef |
| author_sort | Ferid Yaccoubi |
| collection | DOAJ |
| description | Obesity is a global public health concern brought on by a combination of excessive dietary intake, inactivity and genetic predisposition. Pyridopyrimidines have received considerable interest in the development of obesity and diabetes. Mannich reaction was applied on 2-thioxo-pyridopyrimidinone derivative with a variety of aromatic and heterocyclic aromatic amines and formaldehyde by grinding at 25°C in the presence of HCl to obtain 18 fused thiadiazinones and two bis-fused thiadiazinone derivatives. Additionally, in silico docking was performed to investigate the mode of actions of the 20 synthesized compounds against fat mass and obesity-associated (FTO) protein. The ligand molecules are nicely docked to the target FTO with binding energies (ΔGbind) ranging from −11.6 to −8.0 kcal/mol. Electrostatic potential map of semiempirical optimized compound 16 was performed using Gaussian 03. Interestingly, two bis-fused thiadiazinone derivatives showed marked amelioration of adiposity in the high-fat diet model especially in hepatic and adipose tissues. |
| first_indexed | 2024-04-11T05:21:46Z |
| format | Article |
| id | doaj.art-7735eb88190645fab1c12c797478cbb1 |
| institution | Directory Open Access Journal |
| issn | 1658-3655 |
| language | English |
| last_indexed | 2024-04-11T05:21:46Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Taibah University for Science |
| spelling | doaj.art-7735eb88190645fab1c12c797478cbb12022-12-23T19:40:41ZengTaylor & Francis GroupJournal of Taibah University for Science1658-36552022-12-011611275128610.1080/16583655.2022.2159210Pyrido-pyrimido-thiadiazinones: green synthesis, molecular docking studies and biological investigation as obesity inhibitorsFerid Yaccoubi0Mohamed El-Naggar1Fathy M. Abdelrazek2Sobhi M. Gomha3Mohamed S. Farghaly4Tariq Z. Abolibda5Lobna A. Ali6Aboubakr H. Abdelmonsef7Université de Tunis El Manar, Faculté des Sciences de Tunis, Laboratoire de Chimie Organique Structurale LR99ES14, Campus Universitaire, 2092 Tunis, TunisiaDepatement of Chemistry, Pure and Applied Chemistry Group, Faculty of Sciences, University of Sharjah, Sharjah 27272, UAEChemistry Department, Faculty of Science, Cairo University, Giza 12613, EgyptChemistry Department, Faculty of Science, Cairo University, Giza 12613, EgyptChemistry Department, Faculty of Science, Cairo University, Giza 12613, EgyptDepartment of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi ArabiaCell Biology and Histochemistry, Zoology Department, Faculty of Science, South Valley University, Qena, EgyptChemistry Department, Faculty of Science, South Valley University, 83523 Qena, EgyptObesity is a global public health concern brought on by a combination of excessive dietary intake, inactivity and genetic predisposition. Pyridopyrimidines have received considerable interest in the development of obesity and diabetes. Mannich reaction was applied on 2-thioxo-pyridopyrimidinone derivative with a variety of aromatic and heterocyclic aromatic amines and formaldehyde by grinding at 25°C in the presence of HCl to obtain 18 fused thiadiazinones and two bis-fused thiadiazinone derivatives. Additionally, in silico docking was performed to investigate the mode of actions of the 20 synthesized compounds against fat mass and obesity-associated (FTO) protein. The ligand molecules are nicely docked to the target FTO with binding energies (ΔGbind) ranging from −11.6 to −8.0 kcal/mol. Electrostatic potential map of semiempirical optimized compound 16 was performed using Gaussian 03. Interestingly, two bis-fused thiadiazinone derivatives showed marked amelioration of adiposity in the high-fat diet model especially in hepatic and adipose tissues.https://www.tandfonline.com/doi/10.1080/16583655.2022.2159210PyridopyrimidinesMannich reactionmulticomponent reactionsmolecular dockingbinding energyobesity |
| spellingShingle | Ferid Yaccoubi Mohamed El-Naggar Fathy M. Abdelrazek Sobhi M. Gomha Mohamed S. Farghaly Tariq Z. Abolibda Lobna A. Ali Aboubakr H. Abdelmonsef Pyrido-pyrimido-thiadiazinones: green synthesis, molecular docking studies and biological investigation as obesity inhibitors Journal of Taibah University for Science Pyridopyrimidines Mannich reaction multicomponent reactions molecular docking binding energy obesity |
| title | Pyrido-pyrimido-thiadiazinones: green synthesis, molecular docking studies and biological investigation as obesity inhibitors |
| title_full | Pyrido-pyrimido-thiadiazinones: green synthesis, molecular docking studies and biological investigation as obesity inhibitors |
| title_fullStr | Pyrido-pyrimido-thiadiazinones: green synthesis, molecular docking studies and biological investigation as obesity inhibitors |
| title_full_unstemmed | Pyrido-pyrimido-thiadiazinones: green synthesis, molecular docking studies and biological investigation as obesity inhibitors |
| title_short | Pyrido-pyrimido-thiadiazinones: green synthesis, molecular docking studies and biological investigation as obesity inhibitors |
| title_sort | pyrido pyrimido thiadiazinones green synthesis molecular docking studies and biological investigation as obesity inhibitors |
| topic | Pyridopyrimidines Mannich reaction multicomponent reactions molecular docking binding energy obesity |
| url | https://www.tandfonline.com/doi/10.1080/16583655.2022.2159210 |
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