Anthracene-9,10-diones as Potential Anticancer Agents:  Bacterial Mutation Studies of Amido-Substituted Derivatives Reveal an Unexpected Lack of Mutagenicity

Journal of Medicinal Chemistry
1998.0

Abstract

Fifteen anthracene-9,10-dione ("anthraquinone") derivatives with (omega-aminoalkyl)carboxamido substituents at the 1-, 2-, 1,4-, or 2, 6-ring positions were tested for bacterial mutagenicity in reverse-mutation assays using Salmonella typhimurium frameshift strains TA1538, TA98, and TA97a, in the presence and absence of a metabolic activation system prepared from the livers of rats treated with Aroclor 1254. Six of the compounds were also tested in S. typhimurium TA100 and Escherichia coli WP2uvrApKM101 strains, which carry mutations particularly sensitive to reversion by DNA base-pair substitution. Two structurally related compounds, mitoxantrone and bisantrene, were tested in parallel as positive controls. Mitoxantrone was mutagenic to S. typhimurium TA1538 and TA98, whereas bisantrene was weakly mutagenic to both these strains but strongly mutagenic toward the TA97a variant. By contrast, although they are also DNA-binding intercalators, none of the amide-functionalized anthracene-9,10-diones of the present study showed significant mutagenic activity in any of the bacterial strains examined. Further, neither substituent position nor systematic alterations in the nature of attached side chains appeared to induce mutagenicity with these agents, although other studies have shown that such structural factors markedly influence their cytotoxic potencies toward mammalian cells in vitro.

Knowledge Graph

Similar Paper

Anthracene-9,10-diones as Potential Anticancer Agents:  Bacterial Mutation Studies of Amido-Substituted Derivatives Reveal an Unexpected Lack of Mutagenicity
Journal of Medicinal Chemistry 1998.0
Anthracene-9,10-diones as potential anticancer agents. Synthesis, DNA-binding, and biological studies on a series of 2,6-disubstituted derivatives
Journal of Medicinal Chemistry 1992.0
6,9-Bis[(aminoalkyl)amino]benzo[g]isoquinoline-5,10-diones. A Novel Class of Chromophore-Modified Antitumor Anthracene-9,10-diones: Synthesis and Antitumor Evaluations
Journal of Medicinal Chemistry 1994.0
Synthesis and antineoplastic evaluations of 1,4-bis(aminoalkanamido)-9,10-anthracenediones
Journal of Medicinal Chemistry 1988.0
Chromophore-Modified Antitumor Anthracenediones: Synthesis, DNA Binding, and Cytotoxic Activity of 1,4-Bis[(aminoalkyl)amino]benzo[g]phthalazine-5,10-diones
Journal of Medicinal Chemistry 1995.0
Synthesis of unsymmetrically substituted 1,4-bis[(aminoalkyl)amino]anthracene-9,10-diones as potential antileukemic agents
Journal of Medicinal Chemistry 1989.0
Potential antitumor agents. 30. Mutagenic activity of some 9-anilinoacridines: relationships between structure, mutagenic potential, and antileukemic activity
Journal of Medicinal Chemistry 1979.0
New hydroxy-amido-anthraquinones as potential antineoplastic drugs.
Bioorganic & Medicinal Chemistry Letters 1992.0
Annulation of substituted anthracene-9,10-diones yields promising selectively antiproliferative compounds
European Journal of Medicinal Chemistry 2013.0
The first series of 4,11-bis[(2-aminoethyl)amino]anthra[2,3-b]furan-5,10-diones: Synthesis and anti-proliferative characteristics
European Journal of Medicinal Chemistry 2011.0