Synthesis and antioxidant properties of novel N-methyl-1,3,4-thiadiazol-2-amine and 4-methyl-2H-1,2,4-triazole-3(4H)-thione derivatives of benzimidazole class

Bioorg Med Chem. 2008 Apr 15;16(8):4294-303. doi: 10.1016/j.bmc.2008.02.077. Epub 2008 Feb 29.

Abstract

Some novel 1-methyl-4-(2-(2-substitutedphenyl-1H-benzimidazol-1-yl)acetyl)thiosemicarbazides (16a-20a), 5-[(2-(substitutedphenyl)-1H-benzimidazol-1-yl)methyl]-N-methyl-1,3,4-thiadiazol-2-amines (17b-20b), and 5-[(2-(substitutedphenyl)-1H-benzimidazol-1-yl)methyl-4-methyl-2H-1,2,4-triazole-3(4H)-thiones (16c-20c) were synthesized and tested for antioxidant properties by using various in vitro systems. Compounds 16a-20a were found to be a good scavenger of DPPH radical (IC(50), 26 microM; IC(50), 30 microM; IC(50), 43 microM; IC(50), 55 microM; IC(50), 74 microM, respectively) when compared to BHT (IC(50), 54 microM). Noteworthy results could not be found on superoxide radical. Compound 19b, which is the most active derivative inhibited slightly lipid peroxidation (28%) at 10(-3)M concentration. Compound 17c inhibited the microsomal ethoxyresorufin O-deethylase (EROD) activity with an IC(50)=4.5 x 10(-4)M which is similarly better than the specific inhibitor caffeine IC(50)=5.2 x 10(-4)M.

MeSH terms

  • Amines / chemistry*
  • Animals
  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / classification
  • Antioxidants / pharmacology*
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / classification
  • Benzimidazoles / pharmacology*
  • Crystallography, X-Ray
  • Free Radicals / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Methylation
  • Models, Molecular
  • Molecular Structure
  • Rats
  • Rats, Wistar
  • Structure-Activity Relationship
  • Thiadiazoles / chemistry*
  • Thiones / chemistry*

Substances

  • Amines
  • Antioxidants
  • Benzimidazoles
  • Free Radicals
  • Thiadiazoles
  • Thiones
  • benzimidazole