Next Article in Journal
Comparison of Sea Snake (Hydrophiidae) Neurotoxin to Cobra (Naja) Neurotoxin
Next Article in Special Issue
Effects of Aflatoxin B1 and Fumonisin B1 on Blood Biochemical Parameters in Broilers
Previous Article in Journal
Actin Crosslinking Toxins of Gram-Negative Bacteria
Previous Article in Special Issue
Cyclopiazonic Acid Biosynthesis of Aspergillus flavus and Aspergillus oryzae
Article Menu

Export Article

Open AccessArticle
Toxins 2009, 1(2), 134-150; doi:10.3390/toxins1020134

Determination of the Biological Activity and Structure Activity Relationships of Drugs Based on the Highly Cytotoxic Duocarmycins and CC-1065

Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37077 Göttingen, Germany
*
Author to whom correspondence should be addressed.
Received: 3 November 2009 / Revised: 28 November 2009 / Accepted: 1 December 2009 / Published: 2 December 2009
(This article belongs to the Special Issue Feature Papers)
View Full-Text   |   Download PDF [289 KB, uploaded 3 December 2009]   |  

Abstract

The natural antibiotics CC-1065 and the duocarmycins are highly cytotoxic compounds which however are not suitable for cancer therapy due to their general toxicity. We have developed glycosidic prodrugs of seco-analogues of these antibiotics for a selective cancer therapy using conjugates of glycohydrolases and tumour-selective monoclonal antibodies for the liberation of the drugs from the prodrugs predominantly at the tumour site. For the determination of structure activity relationships of the different seco-drugs, experiments addressing their interaction with synthetic DNA were performed. Using electrospray mass spectrometry and high performance liquid chromatography, the experiments revealed a correlation of the stability of these drugs with their cytotoxicity in cell culture investigations. Furthermore, it was shown that the drugs bind to AT-rich regions of double-stranded DNA and the more cytotoxic drugs induce DNA fragmentation at room temperature in several of the selected DNA double-strands. Finally, an explanation for the very high cytotoxicity of CC-1065, the duocarmycins and analogous drugs is given. View Full-Text
Keywords: ADEPT; anticancer agents; cancer therapy; CC-1065; cytotoxicity; DNA alkylation; duocarmycins; electrospray mass spectrometry; HPLC; oligonucleotides; structure activity relationship ADEPT; anticancer agents; cancer therapy; CC-1065; cytotoxicity; DNA alkylation; duocarmycins; electrospray mass spectrometry; HPLC; oligonucleotides; structure activity relationship
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Tietze, L.F.; Krewer, B.; Von Hof, J.M.; Frauendorf, H.; Schuberth, I. Determination of the Biological Activity and Structure Activity Relationships of Drugs Based on the Highly Cytotoxic Duocarmycins and CC-1065. Toxins 2009, 1, 134-150.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Toxins EISSN 2072-6651 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top