title: Design, Synthesis, and Evaluation of Diazeniumdiolate-Based DNA Cross-Linking Agents Activatable by Glutathione S-Transferase.
abstract: A novel class of O2-(2,4-dinitrophenyl)-1-[N,N-bis(2-substituted ethyl)amino]diazen-1-ium-1,2-diolates 4-6 were designed, synthesized, and biologically evaluated. The most active compound 6 caused significant DNA damage by releasing N,N-bis(2-TsO ethyl)amine and two molecules of nitric oxide (NO) after activation by GST/GSH in cancer cells, being more cytotoxic against three cancer cell lines than a well-known diazeniumdiolate-based anticancer agent JS-K, suggesting that the strategy has potential to extend to other O2-derived diazeniumdiolates to improve anticancer activity.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening and ‡Foreign Languages Department, China Pharmaceutical University , Nanjing 210009, PR China.
authors.forename: Rongfang
authors.initials: R
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening and ‡Foreign Languages Department, China Pharmaceutical University , Nanjing 210009, PR China.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening and ‡Foreign Languages Department, China Pharmaceutical University , Nanjing 210009, PR China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening and ‡Foreign Languages Department, China Pharmaceutical University , Nanjing 210009, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening and ‡Foreign Languages Department, China Pharmaceutical University , Nanjing 210009, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening and ‡Foreign Languages Department, China Pharmaceutical University , Nanjing 210009, PR China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening and ‡Foreign Languages Department, China Pharmaceutical University , Nanjing 210009, PR China.
authors.forename: Honghua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening and ‡Foreign Languages Department, China Pharmaceutical University , Nanjing 210009, PR China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Jiangsu Key Laboratory of Drug Screening and ‡Foreign Languages Department, China Pharmaceutical University , Nanjing 210009, PR China.
authors.forename: Zhangjian
authors.initials: Z
authors.lastname: Huang