title: Synthesis and biological evaluation of Oblongifolin C derivatives as c-Met inhibitors.
abstract: Oblongifolin C, one of the polyprenylated benzoylphloroglucinol natural products (PPAPs) isolated from the fruits of Garcinia yunnanensis Hu, was recently discovered to be a potent anti-tumor agent. A collection of 12 derivatives with modifications on the benzophenone moieties were synthesized and tested for c-Met kinase inhibition and cytotoxicity against the HepG2, Miapaca-2, HCC827, Hela, A549, AGS, and HT-29 cell lines in vitro. An oxidized derivative, 10, was found to possess strong inhibition and anti-migration properties in the HCC827 cell line and serves as a potential lead compound for the development of new anticancer drugs. In addition, structure-activity relationships (SAR) were also evaluated to provide key information for future anticancer drug development.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cai Lun Lu 1200, Shanghai 201203, People's Republic of China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cai Lun Lu 1200, Shanghai 201203, People's Republic of China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cai Lun Lu 1200, Shanghai 201203, People's Republic of China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, People's Republic of China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cai Lun Lu 1200, Shanghai 201203, People's Republic of China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, People's Republic of China.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Lao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cai Lun Lu 1200, Shanghai 201203, People's Republic of China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, People's Republic of China.
authors.forename: Changwu
authors.initials: C
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cai Lun Lu 1200, Shanghai 201203, People's Republic of China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, People's Republic of China. Electronic address: ths97029@163.com.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Tan
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Cai Lun Lu 1200, Shanghai 201203, People's Republic of China; Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, People's Republic of China. Electronic address: xuhongxi88@gmail.com.
authors.forename: Hongxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001577:Benzophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D029760:Garcinia / Q000737:chemistry; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001577:Benzophenones; D047428:Protein Kinase Inhibitors; D013729:Terpenes; C575447:oblongifolin C; C047723:benzophenone; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: Cytotoxicity; Derivatives; HCC827 cell line; Modification; Oblongifolin C; Structure–activity relationships; c-Met kinase inhibitor