In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors
Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC<sub>5...
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MDPI AG
2020-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/17/3991 |
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| author | Ninie Nadia Zulkipli Rahimah Zakaria Idris Long Siti Fadilah Abdullah Erma Fatiha Muhammad Habibah A. Wahab Teguh Haryo Sasongko |
| author_facet | Ninie Nadia Zulkipli Rahimah Zakaria Idris Long Siti Fadilah Abdullah Erma Fatiha Muhammad Habibah A. Wahab Teguh Haryo Sasongko |
| author_sort | Ninie Nadia Zulkipli |
| collection | DOAJ |
| description | Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC<sub>50</sub> of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from <i>Centella asiatica</i>, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC<sub>50</sub> values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors. |
| first_indexed | 2024-03-10T16:39:04Z |
| format | Article |
| id | doaj.art-b82222dcceec4d52a95ff5ff6181d779 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T16:39:04Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b82222dcceec4d52a95ff5ff6181d7792023-11-20T12:14:24ZengMDPI AGMolecules1420-30492020-09-012517399110.3390/molecules25173991In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR InhibitorsNinie Nadia Zulkipli0Rahimah Zakaria1Idris Long2Siti Fadilah Abdullah3Erma Fatiha Muhammad4Habibah A. Wahab5Teguh Haryo Sasongko6School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, MalaysiaSchool of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, MalaysiaSchool of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, MalaysiaSchool of Dental Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, MalaysiaSchool of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang 11800, MalaysiaSchool of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang 11800, MalaysiaSchool of Medicine, Perdana University-RCSI, Jalan MAEPS Perdana, Serdang 43400, MalaysiaNatural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC<sub>50</sub> of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from <i>Centella asiatica</i>, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC<sub>50</sub> values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors.https://www.mdpi.com/1420-3049/25/17/3991mammalian target of rapamycin (mTOR)molecular dockingeverolimusasiaticosideasiatic acidIC<sub>50</sub> |
| spellingShingle | Ninie Nadia Zulkipli Rahimah Zakaria Idris Long Siti Fadilah Abdullah Erma Fatiha Muhammad Habibah A. Wahab Teguh Haryo Sasongko In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors Molecules mammalian target of rapamycin (mTOR) molecular docking everolimus asiaticoside asiatic acid IC<sub>50</sub> |
| title | In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors |
| title_full | In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors |
| title_fullStr | In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors |
| title_full_unstemmed | In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors |
| title_short | In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors |
| title_sort | in silico analyses and cytotoxicity study of asiaticoside and asiatic acid from malaysian plant as potential mtor inhibitors |
| topic | mammalian target of rapamycin (mTOR) molecular docking everolimus asiaticoside asiatic acid IC<sub>50</sub> |
| url | https://www.mdpi.com/1420-3049/25/17/3991 |
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