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Microcalorimetric measurements in design of anti-tumor drugs

Jan Mazerski 

Gdansk University of Technology, Department of Pharmaceutical Technology and Biochemistry, ul. Narutowicza 11/12, Gdańsk 80-952, Poland

Abstract

DNA is a molecular target of a majority of known anti-tumor drugs. Inhibition of cell proliferation or cell death might be a result of various mode of action on biochemical as well as cellular level. However, in each case formation of physicochemical ligand-DNA complex is a first step of the drug action. Knowledge about the complex stability as well as about nature of interactions resposible for its formation is crucial for rational design of new drugs with better pharmaceutical properties. Thus, a lot of scientific groups, including Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, develop brought research projects concerning this process. These projects including determination of:

  • 3D structure of complexes
  • ligand sequential selectivity
  • nature of interactions responsible for the complex formation and its stability
  • influence of medium composition on the complex formation

Different spectral techniques are mainly used to determine a ligand ability to formation of the complex. However, interpretation of observed spectral changes needs several assumptions about nature of the complex and obtained thermodynamics data have indirect and partially speculative character.

Direct thermodynamics data about the complex formation could be obtained with calorimetric measurements, only. Modern microcalorimeters are able to determine thermal effects on a level of μJ and need relatively small amount of reagents. In addition, direct measure of thermal effects of the complex formation allows to create entirely thermodynamics description including information about nature of interactions responsible for the complex formation. Thus, an application of this techniques rapidly increases.

In this presentation results of microcalorimetric measurements obtained in our Department for selected derivatives and analogs of acridine have been presented together with conclusions come from entirely thermodynamics description. The usefulness of such descriptions for design of new generation of acridine anti-tumor drugs will be also discussed.

 

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Presentation: Oral at VII Multidyscyplinarna Konferencja Nauki o Leku, by Jan Mazerski
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-15 16:30
Revised:   2010-03-15 16:30