期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 51, 期 21, 页码 6761-6772出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm800499x
关键词
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资金
- Spanish MEC [SAF 2006-06720]
- ICIC (Instituto Canario de Investigacion del Cancer)
- FIS [P106/1211]
- Spanish Ministry of Science Technology
- MEC
On the basis of previous pharmacophore modeling studies of naphthoquinones derivatives, we have desioned and synthesized a new set of pyranonaphthoquinones. These compounds were obtained through a direct and highly efficient approach based on an intramolecular domino Knoevenagel hetero Diels-Alder reaction from lawsone (2-hydroxynaphthoquinone) and a variety of aldehydes containing an alkene. The synthesized pyranonaphthoquinones were evaluated against the a isoform of human topoisomerase II (hTopoII alpha). Among the 11 derivatives studied, we found that six of them act as catalytic inhibitors of the enzyme in vitro. These six derivatives strongly preclude the enzyme from decatenating or relaxing suitable substrates. Finally, we correlate their active/inactive status with docking studies of these novel compounds into the ATPase domain of hTopoII alpha.
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