New artesunic acid homodimers: potent reversal agents of multidrug resistance in leukemia cells.

Abstract

To evade the problem of multidrug resistance, hybridization of natural products in dimers is considered as an effective method. After the successful synthesis of three artesunic acid homodimers connected by different types of chemical linkers, we analyzed their activity against human CCRF-CEM and multidrug-resistant P-glycoprotein-overexpressing CEM/ADR 5000 leukemia cells and observed, that multidrug resistant cells were not cross-resistant to the new compounds. Collateral sensitivity was observed for artesunic acid homodimer 2. The obtained results deliver valuable information about the linker's structure which is required for homodimers to be highly cytotoxic.

• Authors: Christoph Reiter, Astrid Herrmann, Aysun Çapci, Thomas Efferth, Svetlana B Tsogoeva
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 20 Issue 18 Pg. 5637-41 (Sep 15 2012) ISSN: 1464-3391 [Electronic] England
• PMID: 22884578 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Artemisinins
• Succinates
• artesunic acid

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Artemisinins (chemical synthesis, chemistry, pharmacology)
• Cell Survival (drug effects)
• Dimerization
• Dose-Response Relationship, Drug
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Drug Screening Assays, Antitumor
• Humans
• Leukemia (drug therapy, pathology)
• Molecular Structure
• Structure-Activity Relationship
• Succinates (chemical synthesis, chemistry, pharmacology)
• Tumor Cells, Cultured