Biological activity of terpene compounds produced by biotechnological methods
Biological activity of terpene compounds produced by biotechnological methods
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DOI：
10.3109/13880209.2015.1103753
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发表时间：
2016-06-02
影响因子：
3.8
通讯作者：
Fiedurek, Jan
中科院分区：
文献类型：
--
作者：
Paduch, Roman;Trytek, Mariusz;Fiedurek, Jan
背景生物转化系统是将具有生物活性的天然化合物结构修饰为有价值的生物活性萜类化合物的有利工具。目的本研究确定了（R）-（+）-柠檬烯和（-）-α-蒎烯及其氧化衍生物（a）紫苏醇和（S）-（+）-和（R）-（-）-香芹酮对映体;（B）芳樟醇、反式马鞭草烯醇和马鞭草烯酮的生物效应。材料与方法本研究采用生物转化法和体外细胞培养试验。将细胞与浓度为5-500 μ g/mL的萜烯一起孵育24小时，用于NR、MTT、DPPH和NO测定。结果经生物转化得到的反式马鞭草烯醇和紫苏醇在较低浓度下即可产生体外抗肿瘤作用（IC 50值分别为77.8和98.8 μ g/mL），（R）-（+）-柠檬烯（IC 50值= 171.4 μ g/mL）和（-）-α-蒎烯（IC 50值= 206.3 μ g/mL）。它们对正常细胞的细胞毒性也较低（IC 50分别> 500和> 200 μ g/mL）。(S)-(+）-香芹酮对肿瘤细胞和正常细胞的毒性分别比（R）-（-）-对映体高59.4%和27.1%。(R)-(在有或无LPS的培养基中，（+）-柠檬烯衍生物降低正常细胞产生IL-6（分别为30.2%和13.9%），而（-）-α-蒎烯衍生物诱导IL-6（马鞭草烯酮具有最强的作用，分别比对照高60.2%和29.1%）。没有萜烯的抗氧化活性低于500 μ g/mL。讨论和结论对肿瘤细胞的生物活性按以下顺序下降：醇>酮>烃。(R)-(（+）-柠檬烯、（-）-α-蒎烯及其衍生物对正常和肿瘤细胞表现出不同的活性，具有明显的对映体差异。
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 (-)-alpha-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 mu g/mL for NR, MTT, DPPH, and NO assays. IL-6 was determined by ELISA with/without 2 h pre-activation with 10 mu g/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 mu g/mL, respectively) than their monoterpene precursors, (R)-(+)-limonene (IC50 value = 171.4 mu g/mL) and (-)-alpha-pinene (IC50 value = 206.3 mu g/mL). They also showed lower cytotoxicity against normal cells (IC50 > 500 and > 200 mu g/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 (-)-alpha-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 mu g/mL.Discussion and conclusions Bioactivity against tumour cells decreased in the following order: alcohols > ketones > hydrocarbons. (R)-(+)-limonene, (-)-alpha-pinene, and their derivatives expressed diverse activity towards normal and tumour cells with noticeable enantiomeric differences.