Annulation of substituted anthracene-9,10-diones yields promising selectively antiproliferative compounds.

Abstract

Anthraquinone derivatives are well-known antiproliferative compounds, and some are currently used in cancer chemotherapy. Some families of annulated anthraquinone analogs have also been examined for antiproliferative activity, but in this regard almost nothing is known of 1-azabenzanthrones (7H-dibenzo[de,h]quinolin-7-ones). A series of 1-azabenzanthrone derivatives, their 2,3-dihydro analogs, and congruently substituted 9,10-anthracenediones were tested against normal human fibroblasts and four human cancer cell lines. Most of the heterocyclic compounds proved to be weakly to moderately antiproliferative with IC50 values extending down to 0.86 μM, and exhibited up to 30-fold selectivity between cancer and normal cells. Both 1-azabenzanthrones and 1-aza-2,3-dihydrobenzanthrones were more potent than their anthraquinone counterparts, and almost without exception, the 2,3-dihydro compounds were more potent than the fully aromatic 1-azabenzanthrones.

• Authors: Vicente Castro-Castillo, Cristian Suárez-Rozas, Natalia Castro-Loiza, Cristina Theoduloz, Bruce K Cassels
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 62 Pg. 688-92 (Apr 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23454511 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Anthraquinones
• Antineoplastic Agents
• 9,10-anthraquinone

Topics

• Anthraquinones (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HL-60 Cells
• Humans
• Molecular Structure
• Structure-Activity Relationship
• Tumor Cells, Cultured