Zuniga Miguel A, Dai Jifeng, Wehunt Mark P, Zhou Qibing
Department of Chemistry, Virginia Commonwealth University, Richmond, 23284-2006, USA.
Chem Res Toxicol. 2006 Jun;19(6):828-36. doi: 10.1021/tx060021s.
Natural terpene quinone methides (QM) and their derivatives have been investigated as therapeutics due to their broad antifungal, antibacterial, and antitumor activities. Recently, we reported that a terpene QM was formed from the catechol precursor through the disproportionation of Cu(II)/(I) redox cycle, and extensive DNA damage was observed throughout the oxidation process. In this paper, we investigate DNA damage with a series of terpene catechols as analogues of natural QM precursors and suggest that reactive oxygen species (ROS) are responsible for the observed DNA damage in the Cu(2+)-induced oxidation despite the stereo- and structural difference of these catechol or subsequent oxidation products. In addition, the presence of NADH significantly enhanced the extent of DNA damage by oxidation of these catechols. Especially with alkene catechols 6-7, the extent of DNA damage was independent of the concentration of catechols, implying that NADH enables the continuous production of ROS through the redox cycle of catechols/quinones.
天然萜类醌甲基化物（QM）及其衍生物因其广泛的抗真菌、抗菌和抗肿瘤活性而被作为治疗药物进行研究。最近，我们报道了一种萜类QM通过铜（II）/（I）氧化还原循环的歧化反应由儿茶酚前体形成，并且在整个氧化过程中观察到广泛的DNA损伤。在本文中，我们以一系列萜类儿茶酚作为天然QM前体的类似物研究DNA损伤，并表明尽管这些儿茶酚或后续氧化产物存在立体和结构差异，但活性氧（ROS）是铜（2+）诱导氧化过程中观察到的DNA损伤的原因。此外，NADH的存在通过这些儿茶酚的氧化显著增强了DNA损伤的程度。特别是对于烯烃儿茶酚6-7，DNA损伤程度与儿茶酚浓度无关，这意味着NADH能够通过儿茶酚/醌的氧化还原循环持续产生活性氧。
