title: Garcinia  xanthones as orally active antitumor agents.
abstract: Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated. A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D₇.₄, aqueous solubility, and permeability at pH 7.4. In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments. The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Haopeng
authors.initials: H
authors.lastname: Sun
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Liu
authors.forename: Shenglie
authors.initials: S
authors.lastname: Zhang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Yang
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
authors.forename: Qidong
authors.initials: Q
authors.lastname: You
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D029760:Garcinia / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D009368:Neoplasm Transplantation; D010539:Permeability; D012995:Solubility; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D044004:Xanthones / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008567:Membranes, Artificial; D044004:Xanthones