Synthesis and cytotoxic activity of non-naturally substituted 4-oxycoumarin derivatives.

Abstract

Coumarins are a large family of natural and synthetic compounds exerting different pharmacological effects, including cytotoxic, anti-inflammatory or antimicrobial. In the present communication we report the synthesis of a series of 12 diversely substituted 4-oxycoumarin derivatives including methoxy substituted 4-hydroxycoumarins, methyl, methoxy or unsubstituted 3-aryl-4-hydroxycoumarins and 4-benzyloxycoumarins and their anti-proliferative effects on breast adenocarcinoma cells (MCF-7), human promyelocytic leukemia cells (HL-60), human histiocytic lymphoma cells (U937) and mouse neuroblastoma cells (Neuro2a). The most potent bioactive molecule was the 4-hydroxy-5,7-dimethoxycoumarin (compound 1) which showed similar potency (IC(50) 0.2-2 μM) in all cancer cell lines tested. This non-natural product reveals a simple bioactive scaffold which may be exploited in further studies.

• Authors: Silvia Serra, Andrea Chicca, Giovanna Delogu, Saleta Vázquez-Rodríguez, Lourdes Santana, Eugenio Uriarte, Laura Casu, Jürg Gertsch
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 22 Issue 18 Pg. 5791-4 (Sep 15 2012) ISSN: 1464-3405 [Electronic] England
• PMID: 22901895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Coumarins

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Coumarins (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• HL-60 Cells
• Humans
• MCF-7 Cells
• Mice
• Molecular Structure
• Stereoisomerism
• Structure-Activity Relationship
• U937 Cells