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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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
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| Series: | Diseases |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-9721/13/5/140 |
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| Summary: | 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. |
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| ISSN: | 2079-9721 |