A Useful Synthesis of 2-Acylamino-1,3,4-oxadiazoles from Acylthiosemicarbazides Using Potassium Iodate and the Discovery of New Antibacterial Compounds

Molecules. 2019 Apr 16;24(8):1490. doi: 10.3390/molecules24081490.

Abstract

A useful method for the synthesis of 2-acylamino-1,3,4-oxadiazoles was developed. By using potassium iodate as an oxidant in water at 60 °C, a wide range of 2-acylamino-1,3,4-oxadiazoles were afforded in moderate to excellent yields within two hours. This method could provide a facile shortcut to generate a series of 2-acylamino-1,3,4-oxadiazoles in medicinal chemistry. Interestingly, some highly potent antibiotic compounds were found through this synthetic method, and some of them displayed a significant improvement in activity compared with the corresponding 1,4-diacylthiosemicarbazides. Compound 2n was the most active against Staphylococcus aureus with MIC (minimum inhibitory concentration) of 1.56 mg/mL, and compounds 2m and 2q were the most active against Bacillus subtilis with MIC of 0.78 mg/mL. The preliminary cytotoxic activities of the most potent compounds 2m, 2n, and 2q against the androgen-independent (PC-3) prostate cancer cell line were more than 30 μM (IC50 > 30 μM).

Keywords: 2-acylamino-1,3,4-oxadiazoles; antibacterial; heterocycles; synthetic method.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects
  • Chemistry Techniques, Synthetic
  • Humans
  • Iodates / chemistry*
  • Microbial Sensitivity Tests
  • Oxadiazoles / chemical synthesis*
  • Oxadiazoles / pharmacology*
  • Potassium Compounds / chemistry*
  • Semicarbazides / chemistry*

Substances

  • Anti-Bacterial Agents
  • Iodates
  • Oxadiazoles
  • Potassium Compounds
  • Semicarbazides
  • 1,3,4-oxadiazole
  • thiosemicarbazide
  • potassium iodate