PCSK9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from Aaptos aaptos and Acanthaster planci as a potential treatment for atherosclerosis.
Atherosclerosis is an inflammatory disorder of the vasculature and one of the underlying causes of cardiovascular diseases. Numerous preventative and therapeutic approaches are being explored to limit the morbidity and mortality of this disease. Nevertheless, some of the treatments cost greatly and...
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| Format: | Article |
| Language: | English |
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Open Science Publishers LLP Inc.
2020
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| Online Access: | https://umpir.ump.edu.my/id/eprint/29272/ |
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| author | Habsah, Mohamad Muhamad Fadzli, Abd Razak Nurjannatul Naim, Kamaruddin Lukman Hakimi, Ab Wahab Asnuzilawati, Asari Yosie, Andriani Siti Fatimah Zaharah, Mohd Fuzi Jasnizat, Saidin Mohd Fadhlizil Fasihi, Mohd Aluwi Jalifah, Latip Tengku Sifzizul, Tengku Muhammad |
| author_facet | Habsah, Mohamad Muhamad Fadzli, Abd Razak Nurjannatul Naim, Kamaruddin Lukman Hakimi, Ab Wahab Asnuzilawati, Asari Yosie, Andriani Siti Fatimah Zaharah, Mohd Fuzi Jasnizat, Saidin Mohd Fadhlizil Fasihi, Mohd Aluwi Jalifah, Latip Tengku Sifzizul, Tengku Muhammad |
| author_sort | Habsah, Mohamad |
| building | UMP Institutional Repository |
| collection | Online Access |
| description | Atherosclerosis is an inflammatory disorder of the vasculature and one of the underlying causes of cardiovascular diseases. Numerous preventative and therapeutic approaches are being explored to limit the morbidity and mortality of this disease. Nevertheless, some of the treatments cost greatly and contributed to various side effects; for example, statin therapy is associated with substantial residual cardiovascular risk as well as issues such as tolerability and patientdependent efficacy. Currently, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has been attracting interests in the drug discovery of atherosclerosis treatment, but ezetimibe, a successful PCSK9 inhibitor, is an expensive monoclonal antibody. Thus, exploring new PCSK9 inhibitors is crucial in overcoming this constraint. In the previous work, aaptaminoids and methyl benzoate were isolated from marine sponges Aaptos aaptos and Acanthaster planci, respectively. These compounds enhance the transcription of the peroxisome proliferator-activated receptor gamma (PPARγ) in the luciferase assay. PPARγ agonist was hypothesized to inhibit the expression of the PCSK9 gene because the former is a transcription factor toward the latter. The synthesis of three aaptaminoids and 11 methyl benzoate derivative was carried out to address its potential as a PCSK9 inhibitor. The structure of the synthesized compound was elucidated using nuclear magnetic resonance spectral and electron impact mass spectral data. The PCSK9 inhibitory
activities were determined by luciferase assay. Four aaptaminoids, such as aaptamine, N1 ,N4 -bisbenzylaaptamine, N4 -[(3,4,5-trimethoxy)benzyl]aaptamine, and N1 -[(3,4,5- trimethoxy)benzyl]aaptamine, and one benzamide derivative, N-(2,3-dihydro-1H-inden-2-yl)-2-methoxybenzamide, were found to inhibit the expression of PCSK9 gene. |
| first_indexed | 2025-11-15T03:58:05Z |
| format | Article |
| id | ump-29272 |
| institution | Universiti Malaysia Pahang |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T03:58:05Z |
| publishDate | 2020 |
| publisher | Open Science Publishers LLP Inc. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | ump-292722025-09-26T02:07:39Z https://umpir.ump.edu.my/id/eprint/29272/ PCSK9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from Aaptos aaptos and Acanthaster planci as a potential treatment for atherosclerosis. Habsah, Mohamad Muhamad Fadzli, Abd Razak Nurjannatul Naim, Kamaruddin Lukman Hakimi, Ab Wahab Asnuzilawati, Asari Yosie, Andriani Siti Fatimah Zaharah, Mohd Fuzi Jasnizat, Saidin Mohd Fadhlizil Fasihi, Mohd Aluwi Jalifah, Latip Tengku Sifzizul, Tengku Muhammad QP Physiology RC Internal medicine RM Therapeutics. Pharmacology RS Pharmacy and materia medica Atherosclerosis is an inflammatory disorder of the vasculature and one of the underlying causes of cardiovascular diseases. Numerous preventative and therapeutic approaches are being explored to limit the morbidity and mortality of this disease. Nevertheless, some of the treatments cost greatly and contributed to various side effects; for example, statin therapy is associated with substantial residual cardiovascular risk as well as issues such as tolerability and patientdependent efficacy. Currently, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has been attracting interests in the drug discovery of atherosclerosis treatment, but ezetimibe, a successful PCSK9 inhibitor, is an expensive monoclonal antibody. Thus, exploring new PCSK9 inhibitors is crucial in overcoming this constraint. In the previous work, aaptaminoids and methyl benzoate were isolated from marine sponges Aaptos aaptos and Acanthaster planci, respectively. These compounds enhance the transcription of the peroxisome proliferator-activated receptor gamma (PPARγ) in the luciferase assay. PPARγ agonist was hypothesized to inhibit the expression of the PCSK9 gene because the former is a transcription factor toward the latter. The synthesis of three aaptaminoids and 11 methyl benzoate derivative was carried out to address its potential as a PCSK9 inhibitor. The structure of the synthesized compound was elucidated using nuclear magnetic resonance spectral and electron impact mass spectral data. The PCSK9 inhibitory activities were determined by luciferase assay. Four aaptaminoids, such as aaptamine, N1 ,N4 -bisbenzylaaptamine, N4 -[(3,4,5-trimethoxy)benzyl]aaptamine, and N1 -[(3,4,5- trimethoxy)benzyl]aaptamine, and one benzamide derivative, N-(2,3-dihydro-1H-inden-2-yl)-2-methoxybenzamide, were found to inhibit the expression of PCSK9 gene. Open Science Publishers LLP Inc. 2020 Article PeerReviewed pdf en cc_by_4 https://umpir.ump.edu.my/id/eprint/29272/1/8.%20PCSK9%20inhibitory%20activity%20of%20marine-derived%20compounds.pdf Habsah, Mohamad and Muhamad Fadzli, Abd Razak and Nurjannatul Naim, Kamaruddin and Lukman Hakimi, Ab Wahab and Asnuzilawati, Asari and Yosie, Andriani and Siti Fatimah Zaharah, Mohd Fuzi and Jasnizat, Saidin and Mohd Fadhlizil Fasihi, Mohd Aluwi and Jalifah, Latip and Tengku Sifzizul, Tengku Muhammad (2020) PCSK9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from Aaptos aaptos and Acanthaster planci as a potential treatment for atherosclerosis. Journal of Applied Pharmaceutical Science, 10 (8). pp. 111-123. ISSN 2231-3354. (Published) https://doi.org/10.7324/JAPS.2020.10813 https://doi.org/10.7324/JAPS.2020.10813 https://doi.org/10.7324/JAPS.2020.10813 |
| spellingShingle | QP Physiology RC Internal medicine RM Therapeutics. Pharmacology RS Pharmacy and materia medica Habsah, Mohamad Muhamad Fadzli, Abd Razak Nurjannatul Naim, Kamaruddin Lukman Hakimi, Ab Wahab Asnuzilawati, Asari Yosie, Andriani Siti Fatimah Zaharah, Mohd Fuzi Jasnizat, Saidin Mohd Fadhlizil Fasihi, Mohd Aluwi Jalifah, Latip Tengku Sifzizul, Tengku Muhammad PCSK9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from Aaptos aaptos and Acanthaster planci as a potential treatment for atherosclerosis. |
| title | PCSK9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from Aaptos aaptos and Acanthaster planci as a potential treatment for atherosclerosis. |
| title_full | PCSK9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from Aaptos aaptos and Acanthaster planci as a potential treatment for atherosclerosis. |
| title_fullStr | PCSK9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from Aaptos aaptos and Acanthaster planci as a potential treatment for atherosclerosis. |
| title_full_unstemmed | PCSK9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from Aaptos aaptos and Acanthaster planci as a potential treatment for atherosclerosis. |
| title_short | PCSK9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from Aaptos aaptos and Acanthaster planci as a potential treatment for atherosclerosis. |
| title_sort | pcsk9 inhibitory activity of marine-derived compounds, aaptaminoids, and benzamide originated from aaptos aaptos and acanthaster planci as a potential treatment for atherosclerosis. |
| topic | QP Physiology RC Internal medicine RM Therapeutics. Pharmacology RS Pharmacy and materia medica |
| url | https://umpir.ump.edu.my/id/eprint/29272/ https://umpir.ump.edu.my/id/eprint/29272/ https://umpir.ump.edu.my/id/eprint/29272/ |