5,7-Dihydroxychromone-2-carboxylic acid and it's transition-metal (Mn and Zn) chelates as non-thiol radioprotective agents

Eur J Med Chem. 2008 Mar;43(3):557-61. doi: 10.1016/j.ejmech.2007.04.013. Epub 2007 May 17.

Abstract

5,7-Dihydroxychromone-2-carboxylic acid (DHCCA) and its related complexes with manganese and zinc were prepared and evaluated for radioprotection activity against gamma irradiation in mice. The LD(50) values were found to be more than 1500 and 1000 mg/kg for DHCCA and it's complexes, respectively. For studying radioprotective effects, 1.0 mmol/kg and 0.5 mmol/kg doses of compounds were administrated subcutaneously 24 h prior to 8.2 Gy gamma irradiation. The percentages of 30-day survival of mice for these compounds were 26%-50%. DHCCA exhibited significant action in delaying deaths as well as effective protection against gamma rays-induced mortality compared to reference drug amifostine. Amifostine provides effective radiation protection when administrated immediately prior to radiation exposure, but administration of DHCCA, even 24 h prior to gamma irradiation, provides a significant protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chelating Agents / chemistry*
  • Chromones / chemistry*
  • Chromones / pharmacology*
  • Chromones / toxicity
  • Drug Design
  • Gamma Rays
  • Magnesium / chemistry*
  • Male
  • Mice
  • Radiation-Protective Agents / chemical synthesis
  • Radiation-Protective Agents / chemistry*
  • Radiation-Protective Agents / pharmacology*
  • Radiation-Protective Agents / toxicity
  • Sulfhydryl Compounds / chemistry
  • Survival Rate
  • Whole-Body Irradiation
  • Zinc / chemistry*

Substances

  • 5,7-dihydroxychromone-2-carboxylic acid
  • Chelating Agents
  • Chromones
  • Radiation-Protective Agents
  • Sulfhydryl Compounds
  • Magnesium
  • Zinc