Syntheses of C-ring modified dehydroabietylamides and their cytotoxic activity

Due to their auspicious pharmacological efficacy as future drug candidates, natural products have been attracting scientific interest for centuries. An interesting field of research concerns the natural product class of terpenes. In this regard, a multitude of studies have already shown their promising biological potential. Therefore, a set of 27 derivatives of the diterpene dehydroabietylamine was synthesized, focusing on C-ring modifications and the derivatization of the amino moiety at C-18. Subsequent screening of the compounds in colorimetric sulforhodamine B-assays revealed an in vitro cytotoxicity especially towards malignant cell line MCF7. Particularly, 12-hydroxy-N-(isonicotinoyl)dehydroabietylamine and N-(4-methoxybenzoyl)dehydroabietylamine showed good cytotoxic activities (EC50 (MCF7) = 4.3 ± 0.2 μM and EC50 (MCF7) = 4.5 ± 1.5 μM, respectively) and significant selectivities (SI = 6.2 and SI = 8.8, respectively) towards malignant cell lines. [Display omitted] •Dehydroabietylamine shows a broad spectrum of biological activities.•“Simple” amides, C-ring-modified and biotinylated amides were prepared.•These compounds were screened in SRB assays for cytotoxic activity.•Several compounds showed high cytotoxicity and good selectivity for human tumor cells.