| Monoterpenes as drug shuttles: cytotoxic (6-aminomethylnicotinate)dichloridoplatinum(II) complexes with potential to overcome cisplatin resistance. | |
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MedLine Citation:
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PMID: 17328536 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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(6-Aminomethylnicotinate)dichloridoplatinum(II) complexes 4 esterified with terpene alcohols were tested on a panel of five human tumor cell lines. While they were accumulated in all cell lines more readily than cisplatin (CDDP), their cytotoxicities were tumor-specific and structure-dependent. Cell lines known to feature elevated levels of antiapoptotic, ion-channel-affecting proteins or otherwise impaired caspase-9 activation responded better to 4 than to CDDP, e.g., the HL-60 leukemia to the fenchyl and bornyl derivatives 4a,b at an IC90 < or = 10 microM. The (-)-menthyl complex 4g was far better accumulated and more efficacious in CDDP-resistant 1411HP male germ cell tumor cells than in the congenerous CDDP-sensitive H12.1 cell line. 4g also broke the CDDP resistance of 518A2 melanoma cells. Cell decay in each case was apoptotic as to TUNEL and Annexin V fluorescence assays. Some complexes 4 seem to positively modulate the permeability of the cell membrane and of blocked mitochondrial anion channels. |
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Authors:
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Rainer Schobert; Bernhard Biersack; Andrea Dietrich; Antje Grotemeier; Thomas Müller; Bernd Kalinowski; Sebastian Knauer; Wieland Voigt; Reinhard Paschke |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-03-01 |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 50 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2007 Mar |
Date Detail:
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Created Date: 2007-03-15 Completed Date: 2007-04-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 1288-93 Citation Subset: IM |
Affiliation:
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Organic Chemistry Laboratory, University of Bayreuth, Universitaetsstrasse 30, 95440 Bayreuth, Germany. Rainer.Schobert@uni-bayreuth.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
/
chemical synthesis,
chemistry,
pharmacology* Apoptosis Cell Line, Tumor Cell Membrane Permeability Cisplatin / pharmacology* DNA / chemistry Drug Resistance, Neoplasm* Drug Screening Assays, Antitumor Electrophoresis, Gel, Two-Dimensional Humans In Situ Nick-End Labeling Male Monoterpenes / chemistry* Necrosis Organoplatinum Compounds / chemical synthesis, chemistry, pharmacology* Plasmids Spectrophotometry, Atomic |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Monoterpenes; 0/Organoplatinum Compounds; 15663-27-1/Cisplatin; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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