title: Xanthone derivatives as potential anti-cancer drugs.
abstract: Xanthone derivatives have been shown to be potent inhibitors of tumour growth. Oxygenated xanthones and [3-(dialkylamino)-2-hydroxypropoxy]xanthones have been prepared and tested for in-vitro inhibition of human PLC/PRF/5, KB and 212 cells. Structure-activity analysis indicated epoxidation of the hydroxyxanthone increased cytotoxicity against tumour cells but ring-opening of the epoxide group with dialkylamine did not enhance the anti-tumour activity. Further evaluation of three of the most active compounds 2, 6-, 3, 6-, and 3, 5-di(2,3-epoxypropoxy)xanthone (compounds 10a, 11a, and 12a, respectively) in DNA, RNA and protein synthesis of tumour cells showed potent inhibitory activity. The 3,5-di(2,3-epoxypropoxy)xanthone also showed potent inhibitory activity against 212 cells, a Ha-ras oncogene-transformed NIH 3T3 cell line. The results indicated that compounds 10a and 12a are potent anti-tumour agents which not only suppressed cellular DNA, RNA and protein synthesis but also specifically inhibited the Ha-ras oncogene in 212 cells.
authors.affiliation: School of Pharmacy, Kaohsiung Medical College, Taiwan, Republic of China.
authors.forename: C N
authors.initials: CN
authors.lastname: Lin
authors.forename: S J
authors.initials: SJ
authors.lastname: Liou
authors.forename: T H
authors.initials: TH
authors.lastname: Lee
authors.forename: Y C
authors.initials: YC
authors.lastname: Chuang
authors.forename: S J
authors.initials: SJ
authors.lastname: Won
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D011905:Genes, ras / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000378:metabolism; D014966:Xanthenes / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D014966:Xanthenes; D008715:Methionine; D013936:Thymidine; D014529:Uridine