title: Naphthazarin derivatives (IV): synthesis, inhibition of DNA topoisomerase I and cytotoxicity of 2- or 6-acyl-5,8-dimethoxy-1, 4-naphthoquinones.
abstract: Some 2- or 6-acyl-5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives were synthesized and evaluated for inhibition of DNA topoisomerase I and cytotoxicity against L1210 cells. Compared with 2-acyl-DMNQ derivatives, 6-acyl-DMNQ compounds, bearing a higher electrophilic quinone moiety, showed a higher potency in the inhibition of DNA topoisomerase I and the cytotoxicity, implying the possible participation of electrophilic arylation in their bioactivities. Time and temperature dependence of the enzyme inhibition suggests that the arylation occurs irreversibly. Among the 6-acyl-DMNQ derivatives, the ones possessing an acyl group of an intermediate size (C(5)-C(9)) showed higher potency in their bioactivities than other derivatives. Furthermore, for the effective inhibition of DNA topoisomerase I, the size of acyl moiety of 6-acylated derivatives seems to be limited to < 12 carbon atoms.
authors.affiliation: College of Pharmacy, Chungnam National University, Taejon, Korea.
authors.forename: G Y
authors.initials: GY
authors.lastname: Song
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: X G
authors.initials: XG
authors.lastname: Zheng
authors.forename: Y J
authors.initials: YJ
authors.lastname: You
authors.forename: H
authors.initials: H
authors.lastname: Cho
authors.forename: J H
authors.initials: JH
authors.lastname: Chung
authors.forename: D E
authors.initials: DE
authors.lastname: Sok
authors.forename: B Z
authors.initials: BZ
authors.lastname: Ahn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: C409448:2-acyl-5,8-dimethoxy-1,4-naphthoquinone; C409447:6-acyl-5,8-dimethoxy-1,4-naphthoquinone; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009285:Naphthoquinones; D059004:Topoisomerase I Inhibitors; C005503:naphthazarin