The role of side chains in the interaction of new antitumor pyrimidoacridinetriones with DNA: Molecular dynamics simulations.

• Authors: Jan Mazerski , Ippolito Antonini , Sante Martelli
• Languages of publication: EN

Abstracts

EN

Pyrimidoacridinetriones (PATs) are a new group of highly active antitumor compounds. It seems reasonable to assume that, like for some other acridine derivatives, intercalation into DNA is a necessary, however not a sufficient condition for antitumor activity of these compounds. Rational design of new compounds of this chemotype requires knowledge about the structure of the intercalation complex, as well as about interactions responsible for its stability. Computer simulation techniques such as molecular dynamics (MD) may provide valuable information about these problems. The results of MD simulations performed for three rationally selected PATs are presented in this paper. The compounds differ in the number and position of side chains. Each of the compounds was simulated in two systems: i) in water, and ii) in the intercalation complex with the dodecamer duplex d(GCGCGCGCGCGC)2. The orientation of the side chain in relation to the ring system is determined by the position of its attachment. Orientation of the ring system inside the intercalation cavity depends on the number and position of side chain(s). The conformations of the side chain(s) of all PATs studied in the intercalation complex were found to be very similar to those observed in water.

Keywords

EN

molecular dynamics simulations; structure of intercalation complex; pyrimidoacridinetrione antitumor agents; role of side chain(s)

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2000
• Volume: 47
• Issue: 1
• Pages: 47-57

Dates

published

2000

received

1999-10-25

Contributors

author

Jan Mazerski

• Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, G. Narutowicza 11/12, 80-952 Gdańsk, Poland

author

Ippolito Antonini

• Department of Chemical Sciences, University of Camerino, 62-032 Camerino (MC), Italy

author

Sante Martelli

• Department of Chemical Sciences, University of Camerino, 62-032 Camerino (MC), Italy

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