Biosynthesis of human diazepam and clonazepam metabolites

Bioorg Med Chem Lett. 2015 Mar 1;25(5):1026-9. doi: 10.1016/j.bmcl.2015.01.025. Epub 2015 Jan 20.

Abstract

A screening of fungal and microbial strains allowed to select the best microorganisms to produce in high yields some of the human metabolites of two benzodiazepine drugs, diazepam and clonazepam, in order to study new pharmacological activities and for chemical standard proposes. Among the microorganisms tested, Cunninghamella echinulata ATCC 9244 and Rhizopus arrhizus ATCC 11145 strains, were the most active producers of the mains metabolites of diazepam which included demethylated, hydroxylated derivatives. Beauveria bassiana ATCC 7159 and Chaetomium indicum LCP 984200 produced the 7 amino-clonazepam metabolite and a product of acid hydrolysis of this benzodiazepine.

Keywords: Benzodiazepines; Demethylation; Filamentous fungi; Hydroxylation; Metabolites; Nitroreduction.

MeSH terms

  • Anticonvulsants / metabolism*
  • Beauveria / metabolism
  • Chaetomium / metabolism
  • Clonazepam / metabolism*
  • Cunninghamella / metabolism
  • Diazepam / metabolism*
  • Fungi / metabolism*
  • Humans
  • Hydrolysis
  • Hydroxylation
  • Industrial Microbiology
  • Methylation
  • Rhizopus / metabolism

Substances

  • Anticonvulsants
  • Clonazepam
  • Diazepam