Flavonoids as dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and in vitro studies
Abstract Background Inflammation is known to involve in many pathological processes of different diseases, but the current therapy causes adverse effects. Thus, there is a great interest for the discovery of flavonoids as a valuable alternative to classical analgesic and anti-inflammatory agent with...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2022-09-01
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| Series: | Beni-Suef University Journal of Basic and Applied Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43088-022-00296-y |
| _version_ | 1818016690503417856 |
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| author | Muhd Hanis Md Idris Siti Norhidayu Mohd Amin Siti Norhidayah Mohd Amin Nyotia Nyokat Heng Yen Khong Manikandan Selvaraj Zainul Amiruddin Zakaria Zurina Shaameri Ahmad Sazali Hamzah Lay Kek Teh Mohd Zaki Salleh |
| author_facet | Muhd Hanis Md Idris Siti Norhidayu Mohd Amin Siti Norhidayah Mohd Amin Nyotia Nyokat Heng Yen Khong Manikandan Selvaraj Zainul Amiruddin Zakaria Zurina Shaameri Ahmad Sazali Hamzah Lay Kek Teh Mohd Zaki Salleh |
| author_sort | Muhd Hanis Md Idris |
| collection | DOAJ |
| description | Abstract Background Inflammation is known to involve in many pathological processes of different diseases, but the current therapy causes adverse effects. Thus, there is a great interest for the discovery of flavonoids as a valuable alternative to classical analgesic and anti-inflammatory agent with dual-inhibitory action, especially on both COX-2 and 5-LOX which can minimize or overcome this problem. Results In the present work, drug-likeness properties of the synthesized flavonoids via Lipinski’s Rule of Five were predicted using QikProp prior to evaluation of their COX and LOX inhibitory activities using enzyme assays. Subsequently, molecular docking was performed using GLIDE to analyse their binding behaviour. The results showed that all compounds obeyed the Lipinski’s Rule of Five. NPC6 and NPC7 had displayed better selectivity towards COX-2 as compared to Indomethacin with less than 50% inhibition against COX-1. In addition, these compounds also inhibited activity of 5-LOX. Their selectivity to COX-2 was due to the binding to hydrophobic region and extends to lobby region near the entrance of COX binding site forming hydrogen bond with Ser530. Interestingly, these compounds showed a similar binding mode as Zileuton in the active site of 5-LOX and formed hydrogen bond interaction with Ala424. Conclusion NPC6 and NPC7 had potential as dual inhibitor of COX-2 and 5-LOX. The scaffolds of these chemical entities are useful to be as lead compounds for the dual inhibition of COX-2 and 5-LOX. |
| first_indexed | 2024-04-14T07:16:10Z |
| format | Article |
| id | doaj.art-96264fcf9d9b45e9ac6cfd2399c2cd30 |
| institution | Directory Open Access Journal |
| issn | 2314-8543 |
| language | English |
| last_indexed | 2024-04-14T07:16:10Z |
| publishDate | 2022-09-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Beni-Suef University Journal of Basic and Applied Sciences |
| spelling | doaj.art-96264fcf9d9b45e9ac6cfd2399c2cd302022-12-22T02:06:18ZengSpringerOpenBeni-Suef University Journal of Basic and Applied Sciences2314-85432022-09-011111910.1186/s43088-022-00296-yFlavonoids as dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and in vitro studiesMuhd Hanis Md Idris0Siti Norhidayu Mohd Amin1Siti Norhidayah Mohd Amin2Nyotia Nyokat3Heng Yen Khong4Manikandan Selvaraj5Zainul Amiruddin Zakaria6Zurina Shaameri7Ahmad Sazali Hamzah8Lay Kek Teh9Mohd Zaki Salleh10Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) SelangorIntegrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) SelangorIntegrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) SelangorFaculty of Applied Sciences, Universiti Teknologi MARA (UiTM) SarawakFaculty of Applied Sciences, Universiti Teknologi MARA (UiTM) SarawakSchool of Engineering, Monash University MalaysiaDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah (UMS)Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM)Faculty of Applied Sciences, Universiti Teknologi MARA (UiTM)Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) SelangorIntegrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) SelangorAbstract Background Inflammation is known to involve in many pathological processes of different diseases, but the current therapy causes adverse effects. Thus, there is a great interest for the discovery of flavonoids as a valuable alternative to classical analgesic and anti-inflammatory agent with dual-inhibitory action, especially on both COX-2 and 5-LOX which can minimize or overcome this problem. Results In the present work, drug-likeness properties of the synthesized flavonoids via Lipinski’s Rule of Five were predicted using QikProp prior to evaluation of their COX and LOX inhibitory activities using enzyme assays. Subsequently, molecular docking was performed using GLIDE to analyse their binding behaviour. The results showed that all compounds obeyed the Lipinski’s Rule of Five. NPC6 and NPC7 had displayed better selectivity towards COX-2 as compared to Indomethacin with less than 50% inhibition against COX-1. In addition, these compounds also inhibited activity of 5-LOX. Their selectivity to COX-2 was due to the binding to hydrophobic region and extends to lobby region near the entrance of COX binding site forming hydrogen bond with Ser530. Interestingly, these compounds showed a similar binding mode as Zileuton in the active site of 5-LOX and formed hydrogen bond interaction with Ala424. Conclusion NPC6 and NPC7 had potential as dual inhibitor of COX-2 and 5-LOX. The scaffolds of these chemical entities are useful to be as lead compounds for the dual inhibition of COX-2 and 5-LOX.https://doi.org/10.1186/s43088-022-00296-yArachidonic acidInflammationChalconeFlavoneFlavanone |
| spellingShingle | Muhd Hanis Md Idris Siti Norhidayu Mohd Amin Siti Norhidayah Mohd Amin Nyotia Nyokat Heng Yen Khong Manikandan Selvaraj Zainul Amiruddin Zakaria Zurina Shaameri Ahmad Sazali Hamzah Lay Kek Teh Mohd Zaki Salleh Flavonoids as dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and in vitro studies Beni-Suef University Journal of Basic and Applied Sciences Arachidonic acid Inflammation Chalcone Flavone Flavanone |
| title | Flavonoids as dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and in vitro studies |
| title_full | Flavonoids as dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and in vitro studies |
| title_fullStr | Flavonoids as dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and in vitro studies |
| title_full_unstemmed | Flavonoids as dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and in vitro studies |
| title_short | Flavonoids as dual inhibitors of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX): molecular docking and in vitro studies |
| title_sort | flavonoids as dual inhibitors of cyclooxygenase 2 cox 2 and 5 lipoxygenase 5 lox molecular docking and in vitro studies |
| topic | Arachidonic acid Inflammation Chalcone Flavone Flavanone |
| url | https://doi.org/10.1186/s43088-022-00296-y |
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