New thiophene-1,2,4-triazole-5(3)-ones: highly bioactive thiosemicarbazides, structures of Schiff bases and triazole-thiols

Eur J Med Chem. 2014 Sep 12:84:639-50. doi: 10.1016/j.ejmech.2014.01.014. Epub 2014 Jan 18.

Abstract

Key compound 2-(4-amino-5-oxo-3-(thiophene-2-ylmethyl)-4,5-dihydro-1,2,4-tiazole-1-yl) acetohydrazide (3) was synthesized by reacting hydrazine hydrate with ethyl-2-(4-amino-5-oxo-3-(thiophene-2-ylmethyl)-4,5-dihydro-1,2,4-tiazole-1yl)acetate (2), obtained in basic media from 4-amino-5-(thiophene-2-ylmethyl)-2H-1,2,4-triazole-3(4H)-one (1). Compound 3 was converted to thiosemicarbazide derivatives (4a-d) and Schiff base derivatives 6a-e and 7a-e. The treatment of compound 4 with NaOH gave 4-amino-2-((4-(4-aryl)-5-mercapto-4H-1,2,4-triazole-3-yl)methyl)-5-(thiophene-2-ylmethyl)-2H-1,2,4-triazole-3(4H)-ones (5a-d). All newly compounds, well characterized by elemental analyses, IR, (1)H NMR, (13)C NMR and mass spectral studies were tested for their antioxidant and antimicrobial activities. Thiosemicarbazide derivatives (4a-d) were highly active in two antioxidant tests with 69.0-88.2% DPPH· scavenging and 503-1257 μM TEAC values, while the others showed lower or no activity. The results of the two antioxidant tests correlated well. Moreover, Thiosemicarbazide derivatives (4a-d) also showed antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Mycobacterium smegmatis. Thiosemicarbazide group deserves attention in the synthesis of bioactive compounds.

Keywords: 1,2,4-Triazole/thiol; Antimicrobial; Antioxidant; Schiff base; Thiosemicarbazide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Bacillus cereus / drug effects
  • Dose-Response Relationship, Drug
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium smegmatis / drug effects
  • Schiff Bases / chemistry*
  • Semicarbazides / chemistry*
  • Staphylococcus aureus / drug effects
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemistry*
  • Thiophenes / chemical synthesis
  • Thiophenes / chemistry
  • Thiophenes / pharmacology*
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Antioxidants
  • Schiff Bases
  • Semicarbazides
  • Sulfhydryl Compounds
  • Thiophenes
  • Triazoles
  • thiosemicarbazide