title: Synthesis and anticancer activities of 3-arylflavone-8-acetic acid derivatives.
abstract: This paper describes the synthesis and the antiproliferative activities of compounds 9a-r, 3-aryl analogs of flavone-8-acetic acid that bear diverse substituents on the benzene rings at the 2- and 3-positions of the flavone nucleus. Their direct and indirect cytotoxicities were evaluated against HT-29 human colon adenocarcinoma cell lines, A549 lung adenocarcinoma cell lines and Human Peripheral Blood Mononuclear Cells (HPBMCs). The results indicate that most of the compounds bearing electron-withdrawing substituents (9b-m) exhibited moderate direct cytotoxicities. And compounds 9e and 9i showed comparable indirect cytotoxicities with 5, 6-dimethylxanthenone-4-acetic acid (DMXAA), and low direct cytotoxicities toward HPBMCs. Interestingly, the compounds 9n-r bearing methoxy groups at the 2- or 3-position of the flavone nucleus exhibited higher indirect cytotoxicities against A549 cell lines than DMXAA, and lower cytotoxicities against HPBMCs. In addition, compounds 9p-r were found to be able to induce tumor necrosis factor α (TNF-α) production in HPBMCs.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Yan
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Bing-Chen
authors.initials: BC
authors.lastname: Ge
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Xiu-Dong
authors.initials: XD
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Jiang-Ping
authors.initials: JP
authors.lastname: Xu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Pei-Liang
authors.initials: PL
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: zhouzz@smu.edu.cn.
authors.forename: Zhong-Zhen
authors.initials: ZZ
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China.
authors.forename: Chun-Qiong
authors.initials: CQ
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address: whchen@smu.edu.cn.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047309:Flavones
keywords: 3-Arylflavone-8-acetic acid; Direct cytotoxicity; Indirect cytotoxicity; Tumor necrosis factor α