Cytotoxic and Anti-Plasmodial Activities of <i>Stephania dielsiana</i> Y.C. Wu Extracts and the Isolated Compounds
Natural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract fr...
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MDPI AG
2020-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/16/3755 |
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| author | James Knockleby Bruno Pradines Mathieu Gendrot Joel Mosnier Thanh Tam Nguyen Thi Thuy Trinh Hoyun Lee Phuong Mai Le |
| author_facet | James Knockleby Bruno Pradines Mathieu Gendrot Joel Mosnier Thanh Tam Nguyen Thi Thuy Trinh Hoyun Lee Phuong Mai Le |
| author_sort | James Knockleby |
| collection | DOAJ |
| description | Natural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract from <i>Stephania dielsiana</i> Y.C. Wu leaves and its isolated compounds. Our study led to the isolation of seven alkaloids, among which oxostephanine (<b>1</b>) is the most active against several cancer cell lines including HeLa, MDA-MB231, MDA-MB-468, MCF-7, and non-cancer cell lines, such as 184B5 and MCF10A, with IC<sub>50</sub> values ranging from 1.66 to 4.35 μM. Morever, oxostephanine (<b>1</b>) is on average two-fold more active against cancer cells than stephanine (<b>3</b>), having a similar chemical structure. Cells treated with oxostephanine (<b>1</b>) are arrested at G2/M cell cycle, followed by the formation of aneuploidy and apoptotic cell death. The G2/M arrest appears to be due, at least in part, to the inactivation of Aurora kinases, which is implicated in the onset and progression of many forms of human cancer. An in-silico molecular modeling study suggests that oxostephanine (<b>1</b>) binds to the ATP binding pocket of Aurora kinases to inactivate their activities. Unlike oxostephanine (<b>1</b>), thailandine (<b>2</b>) is highly effective against only the triple-negative MDA-MB-468 breast cancer cells. However, it showed excellent selectivity against the cancer cell line when compared to its effects on non-cancer cells. Furthermore, thailandine (<b>2</b>) showed excellent anti-plasmodial activity against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 <i>Plasmodium falciparum</i> strains. The structure–activity relationship of isolated compound was also discussed in this study. The results of this study support the traditional use of <i>Stephania dielsiana</i> Y.C. Wu and the lead molecules identified can be further optimized for the development of highly effective and safe anti-cancer and anti-plasmodial drugs. |
| first_indexed | 2024-03-10T17:16:39Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
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| last_indexed | 2024-03-10T17:16:39Z |
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| spelling | doaj.art-d370e36080d34505a8076089a755db7b2023-11-20T10:28:54ZengMDPI AGMolecules1420-30492020-08-012516375510.3390/molecules25163755Cytotoxic and Anti-Plasmodial Activities of <i>Stephania dielsiana</i> Y.C. Wu Extracts and the Isolated CompoundsJames Knockleby0Bruno Pradines1Mathieu Gendrot2Joel Mosnier3Thanh Tam Nguyen4Thi Thuy Trinh5Hoyun Lee6Phuong Mai Le7Health Science North Research Institute, 56 Walford Road, Sudbury, ON P3E 2H2, CanadaDépartement Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, FranceDépartement Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, FranceDépartement Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, 13005 Marseille, FranceGraduate University of Science and Technology and Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Hanoi 70750, VietnamGraduate University of Science and Technology and Institute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Hanoi 70750, VietnamHealth Science North Research Institute, 56 Walford Road, Sudbury, ON P3E 2H2, CanadaNational Research Council Canada, 100 Sussex Drive, Ottawa, ON K1A 0R6, CanadaNatural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract from <i>Stephania dielsiana</i> Y.C. Wu leaves and its isolated compounds. Our study led to the isolation of seven alkaloids, among which oxostephanine (<b>1</b>) is the most active against several cancer cell lines including HeLa, MDA-MB231, MDA-MB-468, MCF-7, and non-cancer cell lines, such as 184B5 and MCF10A, with IC<sub>50</sub> values ranging from 1.66 to 4.35 μM. Morever, oxostephanine (<b>1</b>) is on average two-fold more active against cancer cells than stephanine (<b>3</b>), having a similar chemical structure. Cells treated with oxostephanine (<b>1</b>) are arrested at G2/M cell cycle, followed by the formation of aneuploidy and apoptotic cell death. The G2/M arrest appears to be due, at least in part, to the inactivation of Aurora kinases, which is implicated in the onset and progression of many forms of human cancer. An in-silico molecular modeling study suggests that oxostephanine (<b>1</b>) binds to the ATP binding pocket of Aurora kinases to inactivate their activities. Unlike oxostephanine (<b>1</b>), thailandine (<b>2</b>) is highly effective against only the triple-negative MDA-MB-468 breast cancer cells. However, it showed excellent selectivity against the cancer cell line when compared to its effects on non-cancer cells. Furthermore, thailandine (<b>2</b>) showed excellent anti-plasmodial activity against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 <i>Plasmodium falciparum</i> strains. The structure–activity relationship of isolated compound was also discussed in this study. The results of this study support the traditional use of <i>Stephania dielsiana</i> Y.C. Wu and the lead molecules identified can be further optimized for the development of highly effective and safe anti-cancer and anti-plasmodial drugs.https://www.mdpi.com/1420-3049/25/16/3755<i>Stephania dielsiana</i> Y.C. Wuaporphine alkaloidsAurora kinasecancer cellsmalaria<i>Plasmodium falciparum</i> |
| spellingShingle | James Knockleby Bruno Pradines Mathieu Gendrot Joel Mosnier Thanh Tam Nguyen Thi Thuy Trinh Hoyun Lee Phuong Mai Le Cytotoxic and Anti-Plasmodial Activities of <i>Stephania dielsiana</i> Y.C. Wu Extracts and the Isolated Compounds Molecules <i>Stephania dielsiana</i> Y.C. Wu aporphine alkaloids Aurora kinase cancer cells malaria <i>Plasmodium falciparum</i> |
| title | Cytotoxic and Anti-Plasmodial Activities of <i>Stephania dielsiana</i> Y.C. Wu Extracts and the Isolated Compounds |
| title_full | Cytotoxic and Anti-Plasmodial Activities of <i>Stephania dielsiana</i> Y.C. Wu Extracts and the Isolated Compounds |
| title_fullStr | Cytotoxic and Anti-Plasmodial Activities of <i>Stephania dielsiana</i> Y.C. Wu Extracts and the Isolated Compounds |
| title_full_unstemmed | Cytotoxic and Anti-Plasmodial Activities of <i>Stephania dielsiana</i> Y.C. Wu Extracts and the Isolated Compounds |
| title_short | Cytotoxic and Anti-Plasmodial Activities of <i>Stephania dielsiana</i> Y.C. Wu Extracts and the Isolated Compounds |
| title_sort | cytotoxic and anti plasmodial activities of i stephania dielsiana i y c wu extracts and the isolated compounds |
| topic | <i>Stephania dielsiana</i> Y.C. Wu aporphine alkaloids Aurora kinase cancer cells malaria <i>Plasmodium falciparum</i> |
| url | https://www.mdpi.com/1420-3049/25/16/3755 |
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