Zhou Qibing, Zuniga Miguel A
Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, Virginia 23284, USA.
Chem Res Toxicol. 2005 Feb;18(2):382-8. doi: 10.1021/tx049703a.
Terpene quinone methides have been isolated from natural resources and exhibit broad biological activities against bacteria, fungi, and tumor cells through the reactive quinone methide (QM) moiety. The biological potential of the oxidation of terpene QM precursors, however, has not been assessed even though Cu(2+)-induced oxidation of catechol shows detrimental effects on cells. In this study, a diterpenone catechol was investigated as a precursor of terpene QM under aqueous conditions in the presence of Cu2+. Direct QM formation was implied in the Cu(2+)-induced oxidation through the study of thiol addition using HPLC and ESI-MS analysis. In addition, oxidation of the initial QM adduct to a second-QM intermediate was observed. The direct QM oxidation pathway may be unique for diterpenone catechol in the Cu(2+)-induced oxidation and is an addition to the reported isomerization pathway of o-quinones to QMs. The DNA damage by the Cu(2+)-induced oxidation of diterpenone catechol was assessed on a short duplex DNA target. Both direct DNA cleavage and nucleobase oxidation were observed extensively by in situ-generated hydroxyl radicals.
萜烯醌甲基化物已从自然资源中分离出来，并通过活性醌甲基化物（QM）部分对细菌、真菌和肿瘤细胞表现出广泛的生物活性。然而，尽管铜（II）诱导的儿茶酚氧化对细胞有有害影响，但萜烯QM前体氧化的生物学潜力尚未得到评估。在本研究中，在铜离子存在的水相条件下，研究了一种二萜酮儿茶酚作为萜烯QM的前体。通过使用高效液相色谱（HPLC）和电喷雾电离质谱（ESI-MS）分析研究硫醇加成，暗示了在铜（II）诱导的氧化过程中直接形成QM。此外，还观察到初始QM加合物氧化为二级QM中间体。直接QM氧化途径在铜（II）诱导的氧化中可能是二萜酮儿茶酚所特有的，并且是对已报道的邻醌异构化为QM途径的补充。在短双链DNA靶点上评估了铜（II）诱导的二萜酮儿茶酚氧化对DNA的损伤。原位生成的羟基自由基广泛观察到直接DNA裂解和核碱基氧化。
