Biological activity of terpene compounds produced by biotechnological methods.

Context: Biotransformation systems are profitable tools for structural modification of bioactive natural compounds into valuable biologically active terpenoids.

Objective: This study determines the biological effect of (R)-(+)-limonene and (-)-α-pinene, and their oxygenated derivatives, (a) perillyl alcohol and (S)-(+)- and (R)-(-)-carvone enantiomers and (b) linalool, trans-verbenol and verbenone, respectively, on human colon tumour cells and normal colonic epithelium.

Materials And Methods: Biotransformation procedures and in vitro cell culture tests were used in this work. Cells were incubated for 24 h with terpenes at concentrations of 5-500 μg/mL for NR, MTT, DPPH, and NO assays. IL-6 was determined by ELISA with/without 2 h pre-activation with 10 μg/mL LPS.

Results: trans-Verbenol and perillyl alcohol, obtained via biotransformation, produced in vitro effect against tumour cells at lower concentrations (IC50 value = 77.8 and 98.8 μg/mL, respectively) than their monoterpene precursors, (R)-(+)-limonene (IC50 value = 171.4 μg/mL) and (-)-α-pinene (IC50 value = 206.3 μg/mL). They also showed lower cytotoxicity against normal cells (IC50 > 500 and > 200 μg/mL, respectively). (S)-(+)-Carvone was 59.4% and 27.1% more toxic to tumour and normal cells, respectively, than the (R)-(-)-enantiomer. (R)-(+)-limonene derivatives decreased IL-6 production from normal cells in media with or without LPS (30.2% and 13.9%, respectively), while (-)-α-pinene derivatives induced IL-6 (verbenone had the strongest effect, 60.2% and 29.1% above control, respectively). None of the terpenes had antioxidative activity below 500 μg/mL.

Discussion And Conclusions: Bioactivity against tumour cells decreased in the following order: alcohols > ketones > hydrocarbons. (R)-(+)-limonene, (-)-α-pinene, and their derivatives expressed diverse activity towards normal and tumour cells with noticeable enantiomeric differences.