title: Synthesis, selective cytotoxicities and probable mechanism of action of 7-methoxy-3-arylflavone-8-acetic acids.
abstract: Thirteen new analogues of flavone-8-acetic acid, that is, compounds 10a-m bearing a methoxy group at the 7-position and diverse subsitiuents on the benzene ring at the 2- and 3-positions of flavone nucleus, were synthesized and evaluated for their direct antiproliferative effects on two human tumor cell lines and for their indirect antiproliferative activities in the transwell co-culture system. The results indicated that most of compounds 10a-m showed moderate direct cytotoxicities. Among them, compound 10i exhibited higher direct cytotoxicity and selectivity for both cell lines over BJ human foreskin fibroblast cells than 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Interestingly, compared with DMXAA, compound 10e showed comparable indirect cytotoxicity and higher selectivity. In addition, compound 10e was found to be able to induce tumor necrosis factor α (TNF-α) production in human peripheral blood mononuclear cells.
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors: Zhong-Zhen
authors: ZZ
authors: Zhou
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors: Chun-Ping
authors: CP
authors: Gu
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors: Yan-Hong
authors: YH
authors: Deng
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors: Guang-Hua
authors: GH
authors: Yan
authors: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors: Xiao-Fang
authors: XF
authors: Li
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors: Le
authors: L
authors: Yu
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: whchen@smu.edu.cn.
authors: Wen-Hua
authors: WH
authors: Chen
authors: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: liusw@smu.edu.cn.
authors: Shu-Wen
authors: SW
authors: Liu
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000085:Acetates; D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha
keywords: 3-Arylflavone-8-acetic acid; Direct cytotoxicity; Indirect cytotoxicity; Transwell co-culture system; Tumor necrosis factor α