Naphthazarin derivatives (II) : Formation of glutathione conjugate, inhibition of DNA topoisomerase-I and cytotoxicity

• Published in: Bioorganic & medicinal chemistry letters Vol. 9; no. 16; pp. 2407 - 2412
• Main Authors: SONG, G.-Y, ZHENG, X.-G, YONG KIM, YOU, Y.-J, SOK, D.-E, AHN, B.-Z
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 16-08-1999
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Chemotherapy; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Glutathione - chemistry; Leukemia L1210 - pathology; Medical sciences; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; Pharmacology. Drug treatments; Structure-Activity Relationship; Topoisomerase I Inhibitors; Tumor Cells, Cultured; Antineoplastic agent; Short chain; Cytotoxicity; Isomerases; Structure activity relation; Bicyclic compound; Secondary alcohol; Chemical synthesis; Glutathione; Enzyme; Chain length; Quinone; Rodentia; DNA topoisomerase; Enzyme inhibitor; Condensed benzenic compound; In vitro; Naphthalene derivatives; L1210 cell line; Vertebrata; Mammalia; Side chain; Cell line; Mouse; Conjugated compound
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00397-2

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).