Influence of anticarcinogenic metalloporphyrin Cu(II)TOEPyP(4) on DNA thermostability in vitro

Georgian Med News. 2009 Oct:(175):57-9.

Abstract

The influence of a new anticarcinogenic compound Cu(II)TOEPyP(4) (Cu(II)-Meso-tetra(4-N-oxyethylpyridyl) porphyrin) (the analogue of TMPy4[tetra(N-mrthyl-4-pyridyl)-porphyrin chloride] - an inhibitor of telomerase activity - on the thermostability of calf thymus DNA in vitro has been studied. It has been shown that Cu(II)TOEPyP(4) is a stronger stabilizing DNA agent, which is expressed with an increase of its thermostability by 20 degrees C. It was determined that complex formation does not disturb the DNA double-helix, and the melting enthalpy (DeltaHm) remains unchanged and it is equal to 11.6+/-1.0 cal/gDNA in the range 0.002<r<0.07, but the melting entropy (DeltaSm) decreases because of the sharp increase of helix state entropy due to disorganization of the water molecule ordered structure in the exclusive binding sites of Cu(II)TOEPyP(4) with DNA. This result is extremely important for pharmacology, because many citostatics used at present even in microg quantities damage DNA to a significant degree. Hence, this is the reason for their mutagenicity and carcinogenicity.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Calorimetry
  • Cattle
  • DNA / drug effects*
  • In Vitro Techniques
  • Metalloporphyrins / chemistry
  • Metalloporphyrins / pharmacology*
  • Nucleic Acid Denaturation / drug effects
  • Porphyrins / metabolism
  • Thermal Conductivity*
  • Thymus Gland / cytology*
  • Thymus Gland / drug effects*
  • Thymus Gland / metabolism

Substances

  • Antineoplastic Agents
  • Metalloporphyrins
  • Porphyrins
  • copper tetra(4-N-methylpyridyl)porphine
  • DNA