title: Luteolin from Flos Chrysanthemi and its derivatives: New small molecule Bcl-2 protein inhibitors.
abstract: Over-expression of the Bcl-2 anti-apoptotic proteins is closely related to tumorigenesis and associated with drug resistance. Here we report that luteolin, a main substance found in Flos Chrysanthemi, directly binds to and shows inhibitory activity against the Bcl-2 protein. We studied the binding mode of luteolin and its derivatives with target proteins, their structure-activity relationship, and their effect on the human leukemia cell line HL-60. The results suggest that luteolin and its derivatives with a benzyl group introduced to the B ring, are new small molecule Bcl-2 protein inhibitors, and their anti-tumor activity is likely related to their effect on the Bcl-2 protein.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Can-Hui
authors.initials: CH
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Changhai Hospital, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Chong-Qing
authors.initials: CQ
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Jun-Hang
authors.initials: JH
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
authors.forename: Jia-Guo
authors.initials: JG
authors.lastname: Lv
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address: ltj204@163.com.
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, 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, 325 Guohe Road, Shanghai 200433, China. Electronic address: zhouyoujun@smmu.edu.cn.
authors.forename: You-Jun
authors.initials: YJ
authors.lastname: Zhou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D031202:Chrysanthemum / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D035264:Flowers / Q000737:chemistry*; D018922:HL-60 Cells; D006801:Humans; D047311:Luteolin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D054852:Small Molecule Libraries; D047311:Luteolin
keywords: Anti-tumor; Apoptosis; Bcl-2 protein; Flos Chrysanthemi; Luteolin