Antimicrobial, hemolytic and thrombolytic activities of some new N-substituted-2-({5-[(1E,3E)F-4-(1,3-benzodioxol- 5-yl)-1,3-butadienyl]-1,3,4-oxadiazol-2-yl}sulfanyl) propanamides

  • A Yasir
  • M Jahangir
  • Aziz ur-Rehman
  • S Ishtiaq
  • M Shahid
Keywords: Piper nigrum, Piperine, Propanamide, Hemolytic, Thrombolytic, Black pepper


Purpose: To synthesize and evaluate the bioactivity of some N-substituted-2-({5-[(1E,3E)-4-(1,3- benzodioxol-5-yl)-1,3-butadienyl]-1,3,4-oxadiazol-2-yl}sulfanyl)propanamides (9a-o) of the alkaloid piperine (1) extracted from P. nigrum (black pepper).

Methods: Extract 1 was subjected to basic hydrolysis to obtain piperic acid (2). The heterocyclic 1,3,4- oxadiazole ring was synthesized from 2 through the formation of an ester and carbohydrazide. A series of electrophiles, 8a-o, were synthesized in the presence of 10 % Na2CO3. The final compounds, 9a-o, were synthesized by stirring 5-[(1E,3E)-4-(1,3-benzodioxol-5-yl)-1,3-butadienyl]-1,3,4-oxadiazol-2-thiol (5) and 8a-o in LiH/DMF. Spectral analysis was performed using infrared (FTIR), proton nuclear magnetic resonance (1H-NMR) and electron impact mass spectrometry (EI-MS) to determine the structures of 9a-o. Antimicrobial activity was evaluated as zone of inhibition by disc diffusion method. Hemolytic and thrombolytic activities were determined by measuring absorbance before and after incubation of blood cells with test compound.

Results: Compound 9d strongly inhibited Bacillus subtilis and Escherichia coli with zone of inhibition values of 16 mm for each. The reference drug, rifampicin, showed zone of inhibition of 21 and 23 mm against B. subtilis and E. coli, respectively. Compound 9a strongly inhibited Aspergillus niger with a zone of inhibition of 18 mm compared to the reference drug, fluconazole, with a zone of inhibition of 19mm.

Conclusion: The newly synthesized compounds are more active antimicrobial agents than piperine. Compounds 9a and 9d are the most active.

Keywords: Piper nigrum, Piperine, Propanamide, Hemolytic, Thrombolytic, Black pepper


Journal Identifiers

eISSN: 1596-9827
print ISSN: 1596-5996