Naphthazarin derivatives (II): formation of glutathione conjugate, inhibition of DNA topoisomerase-I and cytotoxicity.
6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones, expressing a higher reactivity in conjugation with glutathione, showed a greater potency in the inhibition of DNA topoisomerase-I and the cytotoxicity against L1210 cells than 2-(1-hydroxyalkyl)-DMNQ derivatives, implying the participation of electrophilic arylation in the bioactivities. In further study 6-(1-Hydroxyalkyl)-5,8-dimethoxy-1,4-naphthoquinones with an alkyl group of shorter chain length (C2-C6) exerted a greater bioactivities than those with longer chain length(>C6).
Song
G Y
GY
College of Pharmacy, Chungnam National University, Taejon, Korea.
Zheng
X G
XG
Kim
Y
Y
You
Y J
YJ
Sok
D E
DE
Ahn
B Z
BZ
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry*; D007939:Leukemia L1210 / Q000473:pathology*; D009285:Naphthoquinones / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009285:Naphthoquinones; D059004:Topoisomerase I Inhibitors; C005503:naphthazarin; D005978:Glutathione