title: Toward a better understanding of the oxaliplatin mode of action upon the steric hindrance of 1,2-diaminocyclohexane and its analogue.
abstract: The present research is concerned with the mechanism investigation on the interaction between oxaliplatin and guanosine 5'-monophosphate (GMP) in the presence of glutathione (GSH). The binding modes of oxaliplatin with GMP and GSH were explored by HPLC and LC-MS techniques, respectively, in which four key intermediates were found and five adducts were determined in the reaction. The results indicated that GSH can interfere with the reaction between oxaliplatin and DNA in two ways. One is by competing with GMP to bind the active platinum unit, and the other is by substituting the guanine-N7 atom of DNA to form inactive platinum species. In contrast to oxaliplatin with trans 1,2-diaminocyclohexane as spatial framework, a known platinum(II) complex, characteristic of trans-bicyclo[2.2.2]octane-7,8-diamine possessing dicyclic steric hindrance, was also studied in the same way to explore its mode of action with DNA.
authors.affiliation: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China; Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, PR China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
authors.forename: Mian
authors.initials: M
authors.lastname: Wu
authors.affiliation: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China; Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, PR China. Electronic address: sgou@seu.edu.cn.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003514:Cyclohexylamines / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C030435:1,2-cyclohexanediamine; D005978:Glutathione
keywords: Glutathione; Guanosine; Oxaliplatin; Steric hindrance