Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options.
Leonotis ocymifolia 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,
Leonotis ocymifolia was studied to find compounds with anticancer activity against TNBC. Methods: Compounds from
Leonotis ocymifolia 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
bis-spirolabdane, 13
S-nepetaefolin (
1), together with five known labdane diterpenoids, namely nepetaefolin (
2), dubiin (
3), nepetaefuran (
4), leonotin (
5), and leonotinin (
6), from the genus
Leonotis were isolated. Overall, the labdane diterpenoids showed selective activity toward triple-negative breast cancer cells (HCC70). Of the compounds extracted, 13
S-nepetaefolin demonstrated the greatest cytotoxic activity with an IC
50 of 24.65 µM (SI = 1.08) against HCC70 cells; however, it was equally cytotoxic to non-tumorigenic MCF-12A breast cells (IC
50 of 26.55 µM), whereas its isomer (
2) showed no activity. This suggests that stereochemistry might have an effect on the cytotoxic activity of the
bis-spirolabdane diterpenoids. All the compounds (
1–
6) demonstrated adsorption, distribution, metabolism, and excretion properties (ADME), while leonotin (
5) and leonotinin (
6) exhibited lead-like properties and high synthetic accessibility scores. Conclusions: The findings from this study warrant further investigation of
L. ocymifolia for potential triple-negative breast cancer (TNBC) therapeutic agents, including potential chemical derivatization of
bis-spiro labdane diterpenoid (
1) to improve selectivity to TNBC over non-cancer cells.
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