title: 2-(1-Oxyalkyl)-1,4-dioxy-9,10-anthraquinones: synthesis and evaluation of antitumor activity.
abstract: Fourty eight derivatives of 2-(1-oxyalkyl)-1,4-dioxy-9,10-anthraquinone were synthesized, and their antitumor activity was evaluated. On the whole, 2-(1-hydroxyalkyl)-1,4-dihydroxy-9,10-anthraquinones (DHAQ = 1,4-dihydroxy-9,10-anthraquinone) showed stronger cytotoxic activity against L1210 cells than 2-(1-hydroxyalkyl)-1,4-dimethoxy-9,10-anthraquinones(DMAQ = 1,4-dimethoxy-9,10-anthraquinone), implying that free hydroxy groups at C-1 and C-4 of the anthraquinone structure are necessary for the cytotoxic activity. The bioactivity of 2-(1-hydroxyalkyl)-DHAQ derivatives differed according to the size of alkyl group at C-1; while the elongation of alkyl group over 7 carbon atoms failed to enhance the bioactivity, the derivatives possessing alkyl moiety of 1-6 carbon atoms showed an increase in the cytotoxicity and the antitumor activity in Sarcoma-180; 2-hydroxymethyl-DHAQ (ED50, 15 micrograms/ml; T/C, 125%), 2-(1-hydroxyethyl)-DHAQ(1.9 micrograms/ml; 139.2%), 2-(1-hydroxypropyl)-DHAQ (7.2 micrograms/ml; 135.1%), 2-(1-hydroxybutyl)-DHAQ (10.2 micrograms/ml; 125.3%), 2-(1-hydroxypentyl)-DHAQ (23.7 micrograms/ml; 110.1%), and 2-(1-hydroxyhexyl)-DHAQ (58 micrograms/ml; 108%). Next, 2-(1-Hydroxyalkyl)-DHAQ derivatives were acetylated to produce 2-(1-acetoxyalkyl)-DHAQ analogues. Although the acetylation somewhat enhanced the cytotoxicity, but not the antitumor action. In addition, the presence of phenyl group at C-1' enhanced the cytotoxicity and the T/C value, compared to alkyl groups of same size; 2-(1-hydroxy-1-phenyl)-DHAQ (ED50, 5.6 micrograms/ml; T/C, 137%).
authors.affiliation: College of Pharmacy, Chungnam National University, Taejon, Korea.
authors.forename: G Z
authors.initials: GZ
authors.lastname: Jin
authors.forename: G Y
authors.initials: GY
authors.lastname: Song
authors.forename: X G
authors.initials: XG
authors.lastname: Zheng
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: D E
authors.initials: DE
authors.lastname: Sok
authors.forename: B Z
authors.initials: BZ
authors.lastname: Ahn
mesh_terms: D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy; D008136:Longevity / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology; D012510:Sarcoma 180 / Q000188:drug therapy; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011809:Quinones