Preparation of divinylsulfone-glutathione adducts and their reactive activities with DNA in vitro
10.3867/j.issn.1000-3002.2017.05.007
- VernacularTitle:二乙烯砜-谷胱甘肽系列加合物的制备及其与体外DNA加合反应活性
- Author:
Shanshan LYU
;
Bin XU
;
Zhongcai GAO
;
Yumei ZHAO
;
Yajiao ZHANG
;
Hua XU
;
Jianfeng WU
;
Jianwei XIE
- Keywords:
divinylsulfone;
glutathione adduct;
DNA adduct
- From:
Chinese Journal of Pharmacology and Toxicology
2017;31(5):422-428
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To prepare the glutathione adducts of divinylsulfone (DVS), which is an important oxidative metabolism product of SM in vivo, and to investigate their reactive capability with DNA in vitro. METHODS The mustard sulfoxide (SMO) and mustard sulfone (SMO2) were prepared by oxidation reaction using HNO3 and KMnO4 as oxidants, respectively. Then, DVS was prepared through dechlorination reaction using CaCO3 under alkaline conditions. Furthermore, the DVS-GSH adduct and DVS-GSH-purine adducts were prepared and identified using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) and nuclear magnetic resonance (NMR). Finally, the adduct reac?tion process of DVS with GSH was monitored using UPLC-MS/MS. RESULTS The DVS-GSH and GSH-DVS-purine adducts were obtained through preparative HPLC and characterized using NMR and high-resolution MS. In aqueous solution, the reactive activity of DVS with GSH was significantly higher than that of SM, and the DVS-GSH adduct had high or reactive activity, which could produce a series of adducts with adenine and guanine in DNA, and the abundance of the adenine adducts was higher than that of the guanine. CONCLUSION DVS-GSH adducts still have high reactive activity with DNA, and more attention should be paid to its potential damage to DNA.
