Labdane Diterpenoids from <i>Leonotis ocymifolia</i> with Selective Cytotoxic Activity Against HCC70 Breast Cancer Cell Line
Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. <i>Leonotis ocymifolia</i> is a shrub widely used in traditional medicine to alleviate cancer-related symptoms. In a search to find safe and efficacious therapeuti...
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2025-05-01
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| author | Jane Busisiwe Ncongwane Vuyelwa Jacqueline Tembu Comfort Mduduzi Nkambule Douglas Kemboi Gerda Fouche Nyeleti Vukea Jo-Anne de la Mare |
| author_facet | Jane Busisiwe Ncongwane Vuyelwa Jacqueline Tembu Comfort Mduduzi Nkambule Douglas Kemboi Gerda Fouche Nyeleti Vukea Jo-Anne de la Mare |
| author_sort | Jane Busisiwe Ncongwane |
| collection | DOAJ |
| description | Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. <i>Leonotis ocymifolia</i> is a shrub widely used in traditional medicine to alleviate cancer-related symptoms. In a search to find safe and efficacious therapeutic agents from medicinal plants, <i>Leonotis ocymifolia</i> was studied to find compounds with anticancer activity against TNBC. Methods: Compounds from <i>Leonotis ocymifolia</i> were characterized using spectroscopic data such as IR, 1D and 2D NMR, and MS spectrometry and evaluated for cytotoxic activity against triple-negative breast cancer (HCC70), hormone receptor-positive breast cancer (MCF-7), and non-tumorigenic mammary epithelial cell lines (MCF-12A). Results: A previously unreported <i>bis</i>-spirolabdane, 13<i>S</i>-nepetaefolin (<b>1</b>), together with five known labdane diterpenoids, namely nepetaefolin (<b>2</b>), dubiin (<b>3</b>), nepetaefuran (<b>4</b>), leonotin (<b>5</b>), and leonotinin (<b>6</b>), from the genus <i>Leonotis</i> were isolated. Overall, the labdane diterpenoids showed selective activity toward triple-negative breast cancer cells (HCC70). Of the compounds extracted, 13<i>S</i>-nepetaefolin demonstrated the greatest cytotoxic activity with an IC<sub>50</sub> of 24.65 µM (SI = 1.08) against HCC70 cells; however, it was equally cytotoxic to non-tumorigenic MCF-12A breast cells (IC<sub>50</sub> of 26.55 µM), whereas its isomer (<b>2</b>) showed no activity. This suggests that stereochemistry might have an effect on the cytotoxic activity of the <i>bis</i>-spirolabdane diterpenoids. All the compounds (<b>1</b>–<b>6</b>) demonstrated adsorption, distribution, metabolism, and excretion properties (ADME), while leonotin (<b>5</b>) and leonotinin (<b>6</b>) exhibited lead-like properties and high synthetic accessibility scores. Conclusions: The findings from this study warrant further investigation of <i>L. ocymifolia</i> for potential triple-negative breast cancer (TNBC) therapeutic agents, including potential chemical derivatization of <i>bis</i>-spiro labdane diterpenoid (<b>1</b>) to improve selectivity to TNBC over non-cancer cells. |
| format | Article |
| id | doaj-art-360c0d65fdf844df823729eb0a54a1d0 |
| institution | Kabale University |
| issn | 2079-9721 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-360c0d65fdf844df823729eb0a54a1d02025-08-20T03:47:48ZengMDPI AGDiseases2079-97212025-05-0113514010.3390/diseases13050140Labdane Diterpenoids from <i>Leonotis ocymifolia</i> with Selective Cytotoxic Activity Against HCC70 Breast Cancer Cell LineJane Busisiwe Ncongwane0Vuyelwa Jacqueline Tembu1Comfort Mduduzi Nkambule2Douglas Kemboi3Gerda Fouche4Nyeleti Vukea5Jo-Anne de la Mare6Department of Chemistry, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South AfricaDepartment of Chemistry, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South AfricaDepartment of Chemistry, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South AfricaDepartment of Chemistry, Tshwane University of Technology, Private Bag X680, Pretoria 0001, South AfricaDepartment of Chemistry, University of Pretoria, Pretoria 0001, South AfricaDepartment of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South AfricaDepartment of Biochemistry and Microbiology, Rhodes University, Grahamstown 6140, South AfricaBackground: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. <i>Leonotis ocymifolia</i> is a shrub widely used in traditional medicine to alleviate cancer-related symptoms. In a search to find safe and efficacious therapeutic agents from medicinal plants, <i>Leonotis ocymifolia</i> was studied to find compounds with anticancer activity against TNBC. Methods: Compounds from <i>Leonotis ocymifolia</i> were characterized using spectroscopic data such as IR, 1D and 2D NMR, and MS spectrometry and evaluated for cytotoxic activity against triple-negative breast cancer (HCC70), hormone receptor-positive breast cancer (MCF-7), and non-tumorigenic mammary epithelial cell lines (MCF-12A). Results: A previously unreported <i>bis</i>-spirolabdane, 13<i>S</i>-nepetaefolin (<b>1</b>), together with five known labdane diterpenoids, namely nepetaefolin (<b>2</b>), dubiin (<b>3</b>), nepetaefuran (<b>4</b>), leonotin (<b>5</b>), and leonotinin (<b>6</b>), from the genus <i>Leonotis</i> were isolated. Overall, the labdane diterpenoids showed selective activity toward triple-negative breast cancer cells (HCC70). Of the compounds extracted, 13<i>S</i>-nepetaefolin demonstrated the greatest cytotoxic activity with an IC<sub>50</sub> of 24.65 µM (SI = 1.08) against HCC70 cells; however, it was equally cytotoxic to non-tumorigenic MCF-12A breast cells (IC<sub>50</sub> of 26.55 µM), whereas its isomer (<b>2</b>) showed no activity. This suggests that stereochemistry might have an effect on the cytotoxic activity of the <i>bis</i>-spirolabdane diterpenoids. All the compounds (<b>1</b>–<b>6</b>) demonstrated adsorption, distribution, metabolism, and excretion properties (ADME), while leonotin (<b>5</b>) and leonotinin (<b>6</b>) exhibited lead-like properties and high synthetic accessibility scores. Conclusions: The findings from this study warrant further investigation of <i>L. ocymifolia</i> for potential triple-negative breast cancer (TNBC) therapeutic agents, including potential chemical derivatization of <i>bis</i>-spiro labdane diterpenoid (<b>1</b>) to improve selectivity to TNBC over non-cancer cells.https://www.mdpi.com/2079-9721/13/5/140<i>Leonotis</i><i>Leonotis ocymifolia</i>labdane diterpenoids<i>bis</i>-spirolabdaneMCF-7HCC70 |
| spellingShingle | Jane Busisiwe Ncongwane Vuyelwa Jacqueline Tembu Comfort Mduduzi Nkambule Douglas Kemboi Gerda Fouche Nyeleti Vukea Jo-Anne de la Mare Labdane Diterpenoids from <i>Leonotis ocymifolia</i> with Selective Cytotoxic Activity Against HCC70 Breast Cancer Cell Line Diseases <i>Leonotis</i> <i>Leonotis ocymifolia</i> labdane diterpenoids <i>bis</i>-spirolabdane MCF-7 HCC70 |
| title | Labdane Diterpenoids from <i>Leonotis ocymifolia</i> with Selective Cytotoxic Activity Against HCC70 Breast Cancer Cell Line |
| title_full | Labdane Diterpenoids from <i>Leonotis ocymifolia</i> with Selective Cytotoxic Activity Against HCC70 Breast Cancer Cell Line |
| title_fullStr | Labdane Diterpenoids from <i>Leonotis ocymifolia</i> with Selective Cytotoxic Activity Against HCC70 Breast Cancer Cell Line |
| title_full_unstemmed | Labdane Diterpenoids from <i>Leonotis ocymifolia</i> with Selective Cytotoxic Activity Against HCC70 Breast Cancer Cell Line |
| title_short | Labdane Diterpenoids from <i>Leonotis ocymifolia</i> with Selective Cytotoxic Activity Against HCC70 Breast Cancer Cell Line |
| title_sort | labdane diterpenoids from i leonotis ocymifolia i with selective cytotoxic activity against hcc70 breast cancer cell line |
| topic | <i>Leonotis</i> <i>Leonotis ocymifolia</i> labdane diterpenoids <i>bis</i>-spirolabdane MCF-7 HCC70 |
| url | https://www.mdpi.com/2079-9721/13/5/140 |
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