Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation
The discovery of potent inhibitors of prostaglandin E2 (PGE2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a vast array of biological signals and physiological events that contributes to i...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014
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| Online Access: | http://psasir.upm.edu.my/id/eprint/34213/ http://psasir.upm.edu.my/id/eprint/34213/1/Inhibition%20of%20prostaglandin%20E2%20production%20by%20synthetic%20minor%20prenylated%20chalcones%20and%20flavonoids.pdf |
| _version_ | 1848847707765997568 |
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| author | Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Mohd Yamin, Bohari Abdul Bahari, Mohammad Nazri Leong, Sze Wei Ahmad, Syahida Abas, Faridah Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai |
| author_facet | Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Mohd Yamin, Bohari Abdul Bahari, Mohammad Nazri Leong, Sze Wei Ahmad, Syahida Abas, Faridah Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai |
| author_sort | Rullah, Kamal |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | The discovery of potent inhibitors of prostaglandin E2 (PGE2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a vast array of biological signals and physiological events that contributes to inflammatory diseases such as rheumatoid arthritis, atherosclerosis, cancer, and pain. In this Letter, we report the synthesis of a series of minor prenylated chalcones and flavonoids which was found to be significantly active in suppressing the PGE2 production secreted by lipopolysaccharide-induced mouse macrophage cells (RAW 264.7). Among the compounds tested, 14b showed a dose-response inhibition of PGE2 production with an IC50 value of 2.1 μM. The suppression upon PGE2 secretion was not due to cell death since 14b did not reduce the cell viability in close proximity to the PGE2 inhibition concentration. The obtained atomic coordinates for the single-crystal XRD of 14b was then applied in the docking simulation to determine the potential important binding interactions with murine COX-2 and mPGES-1 putative binding sites. |
| first_indexed | 2025-11-15T09:22:53Z |
| format | Article |
| id | upm-34213 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T09:22:53Z |
| publishDate | 2014 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-342132018-02-07T06:07:27Z http://psasir.upm.edu.my/id/eprint/34213/ Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Mohd Yamin, Bohari Abdul Bahari, Mohammad Nazri Leong, Sze Wei Ahmad, Syahida Abas, Faridah Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai The discovery of potent inhibitors of prostaglandin E2 (PGE2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a vast array of biological signals and physiological events that contributes to inflammatory diseases such as rheumatoid arthritis, atherosclerosis, cancer, and pain. In this Letter, we report the synthesis of a series of minor prenylated chalcones and flavonoids which was found to be significantly active in suppressing the PGE2 production secreted by lipopolysaccharide-induced mouse macrophage cells (RAW 264.7). Among the compounds tested, 14b showed a dose-response inhibition of PGE2 production with an IC50 value of 2.1 μM. The suppression upon PGE2 secretion was not due to cell death since 14b did not reduce the cell viability in close proximity to the PGE2 inhibition concentration. The obtained atomic coordinates for the single-crystal XRD of 14b was then applied in the docking simulation to determine the potential important binding interactions with murine COX-2 and mPGES-1 putative binding sites. Elsevier 2014-08-15 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/34213/1/Inhibition%20of%20prostaglandin%20E2%20production%20by%20synthetic%20minor%20prenylated%20chalcones%20and%20flavonoids.pdf Rullah, Kamal and Mohd Aluwi, Mohd Fadhlizil Fasihi and Mohd Yamin, Bohari and Abdul Bahari, Mohammad Nazri and Leong, Sze Wei and Ahmad, Syahida and Abas, Faridah and Ismail, Nor Hadiani and Jantan, Ibrahim and Lam, Kok Wai (2014) Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation. Bioorganic & Medicinal Chemistry Letters, 24 (16). pp. 3826-3834. ISSN 0960-894X; ESSN: 1464-3405 http://www.sciencedirect.com/science/article/pii/S0960894X14006891 10.1016/j.bmcl.2014.06.061 |
| spellingShingle | Rullah, Kamal Mohd Aluwi, Mohd Fadhlizil Fasihi Mohd Yamin, Bohari Abdul Bahari, Mohammad Nazri Leong, Sze Wei Ahmad, Syahida Abas, Faridah Ismail, Nor Hadiani Jantan, Ibrahim Lam, Kok Wai Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation |
| title | Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation |
| title_full | Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation |
| title_fullStr | Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation |
| title_full_unstemmed | Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation |
| title_short | Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation |
| title_sort | inhibition of prostaglandin e2 production by synthetic minor prenylated chalcones and flavonoids: synthesis, biological activity, crystal structure, and in silico evaluation |
| url | http://psasir.upm.edu.my/id/eprint/34213/ http://psasir.upm.edu.my/id/eprint/34213/ http://psasir.upm.edu.my/id/eprint/34213/ http://psasir.upm.edu.my/id/eprint/34213/1/Inhibition%20of%20prostaglandin%20E2%20production%20by%20synthetic%20minor%20prenylated%20chalcones%20and%20flavonoids.pdf |