title: Structural modification of luteolin from Flos Chrysanthemi leads to increased tumor cell growth inhibitory activity.
abstract: The luteolin from Flos Chrysanthemi was found to directly bind to the Bcl-2 protein and inhibit the tumor cell growth in our previous study. However, it has been shown to possess wide and week biological activities. In this study, a series of derivatives of luteolin were designed and synthesized, and their tumor cell growth inhibitory activities were evaluated against human leukemia cell line HL-60. The results showed that compounds 1B-2, 2A-3, and 2B-5, with hydrophobic substituted benzyl groups introduced to B ring and hydrogen or methyl introduced to 7-OH group of luteolin, exhibited the strongest inhibitory activity with the IC50 lower than 10μM, which were significantly more potent than luteolin. The studies presented here offer a good example for modifications of flavones to improve their tumor cell growth inhibitory activities.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Shihai
authors.initials: S
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
authors.forename: Mingping
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Song
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Shen
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: zhouyoujun@smmu.edu.cn.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: zhuju@smmu.edu.cn.
authors.forename: Ju
authors.initials: J
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: canhuizheng@smmu.edu.cn.
authors.forename: Canhui
authors.initials: C
authors.lastname: Zheng
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D031202:Chrysanthemum / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D047311:Luteolin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047311:Luteolin
keywords: Anti-tumor; Bcl-2 protein; Flos Chrysanthemi; Luteolin; Structural modification