title: Synthesis and cytotoxicity evaluation of 3-amino-2-hydroxypropoxyisoflavone derivatives.
abstract: Soy isoflavones exert a wide variety of biological activities, such as antioxidant, anti-inflammatory and anti-cancer properties. Nuclear factor erythroid 2-related factor 2 (Nrf2), a bZip transcription factor, plays a key role in soy isoflavones induced protection against oxidative stress and cancer. To obtain more effective isofavones, a series of 7,4'-bis-(3-amino-2-hydroxypropoxy), 7 or 4'-(3-amino-2-hydroxypropoxy) isoflavone derivatives have been synthesized as potential antitumor agents and Nrf2/ARE (antioxidant response element) activators. The cytotoxicity of these compounds in human cancer cell lines MDA-MB-231, HT-29, HCT116, HepG2 and 7402 was tested by MTT assay. In this study, the cytotoxicity of compound 3b exhibited highest cytotoxic activity and at the safety dose range, it also strongly up-regulated antioxidant response element (ARE)-luciferase reporter activity. In addition, compound 3b induced Nrf2 nuclear translocation and upregulated its downstream target genes NQO-1 and HO-1 at protein level. Taken together, our results suggest that compound 3b could be a potential agent for cancer themotherapy or cancer chemoprevention.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Jiangsu Nanjing, 210009, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Tang
authors.affiliation: Department of Organic Chemistry, China Pharmaceutical University, Jiangsu Nanjing 210009, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Jiangsu Nanjing, 210009, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Organic Chemistry, China Pharmaceutical University, Jiangsu Nanjing 210009, China.
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Zheng
authors.affiliation: Department of Organic Chemistry, China Pharmaceutical University, Jiangsu Nanjing 210009, China. Electronic address: L_John81@sina.com.
authors.forename: Jin-Rong
authors.initials: JR
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Jiangsu Nanjing, 210009, China. Electronic address: ronghu@cpu.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007529:Isoflavones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007529:Isoflavones; D051267:NF-E2-Related Factor 2
keywords: Anti-cancer; Chemoprevention; Cytotoxicity; Isoflavone; Nrf2/ARE