2-Substituted naphthazarins; synthesis and antitumor activity.
|
| Abstract |
A series of 2-substituted naphthazarin derivatives, 5,8-dihydroxy-1,4-naphthoquinone (DHNQ) derivatives and 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives, were synthesized, and their cytotoxic activity against some cancer cell lines and antitumor action against S-180 tumor were evaluated. In general, 2-(1-hydroxyalkyl)-DHNQ derivatives showed a higher cytotoxicity than 2-(1-hydroxyalkyl)-DMNQ derivatives, implying a predominant role of redox cycling rather than electrophilicity in cytotoxicity. 2-(1-Alkoxy-4-methylpentyl) or 2-(1-acyloxy-4-methylpentyl) derivatives were produced by alkylation or acylation at the C-1' position of 2-(1-hydroxy-4-methylpentyl)-DHNQ or DMNQ derivatives. Although the cytotoxicity differed according to the size of the alkyl or acyl chain, alkylation or acylation at the C-1' position did not improve the cytotoxicity remarkably, and DHNQ derivatives were still more cytotoxic than DMNQ derivatives. Separately, in vivo testing showed that 2-(1-acyloxyalkyl)-DHNQ derivatives or 2-(1-alkoxyalkyl)-DHNQ derivatives expressed a higher antitumor action than 2-(1-hydroxyalkyl)-DMNQ or -DHNQ derivatives in contrast to the cytotoxicity observations. The total size of two side chains at C-1' seemed to govern the antitumor activity, with 9 to 11 carbon atoms being optimal. Thus, it is suggested that the physical properties as well as the chemical reactivity are to be considered in relation to the antitumor action of 2-substituted naphthazarin compounds.
|
|---|---|
| Authors | B Kyong-Up, S G Yong, K Yong, S Dai-Eun, A Byung-Zun |
| Journal | Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 330 Issue 12 Pg. 377-82 (Dec 1997) ISSN: 0365-6233 [Print] Germany |
| PMID | 9474896 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!