Studies on quinones. Part 41: Synthesis and cytotoxicity of isoquinoline-containing polycyclic quinones

The regioselective synthesis of fused isoquinolinequinones (i.e., 6, 8, 13, and 15) through highly regiocontrolled cycloaddition reactions from methyl 1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate 3 and 1,3-dienes is reported. The 2-aza- and 1,6-diaza-anthraquinone derivatives display...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2006-07, Vol.14 (14), p.5003-5011
Main Authors: Valderrama, Jaime A., González, M. Florencia, Pessoa-Mahana, David, Tapia, Ricardo A., Fillion, Houda, Pautet, Felix, Rodriguez, Jaime A., Theoduloz, Cristina, Schmeda-Hirschmann, Guillermo
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Aza-anthraquinones
Biological and medical sciences
Cell Line
Cell Line, Tumor
Cytotoxicity
Diels–Alder reaction
Drug Design
Drug Screening Assays, Antitumor
Etoposide - pharmacology
Fibroblasts - drug effects
General aspects
Humans
Medical sciences
Pharmacology. Drug treatments
Quinones - chemical synthesis
Quinones - chemistry
Quinones - pharmacology
Regioselectivity
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Summary:The regioselective synthesis of fused isoquinolinequinones (i.e., 6, 8, 13, and 15) through highly regiocontrolled cycloaddition reactions from methyl 1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate 3 and 1,3-dienes is reported. The 2-aza- and 1,6-diaza-anthraquinone derivatives displayed significant in vitro activity on normal fibroblast and four tumor cell lines. In the search for new potentially anticancer drugs, isoquinolinequinone-containing polycyclic compounds have been designed and synthesized through highly regiocontrolled cycloaddition reactions of methyl 1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate with polarized 1,3-dienes and a thiazole- o-quinodimethane. The new N-heterocyclic quinones were tested on normal human fibroblasts and four distinct human cancer cell lines. Two of the evaluated compounds displayed significant in vitro activity (IC 50: 0.44–5.9 μM) comparable to that of the reference drug etoposide.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2006.03.008