Purpose: To synthesize some acetamide derivatives bearing azinane and 1,3,4-oxadiazole heterocyclic
cores and to evaluate their antibacterial potentials.
Methods: Ethyl piperidin-4-carboxylate (
2) was converted to ethyl 1-[(4-chlorophenyl)sulfonyl]piperidin-4-carboxylate (
3), 1-[(4-chlorophenyl)sulfonyl]piperidin-4-carbohydrazide (
4) and 5-[1-(4-chlorophenylsulfonyl)-4-piperidinyl]-1,3,4-oxadiazol-2-thiol (
5) using three consecutive steps. The target
molecules, 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-{[N-(substituted)-2-acetamoyl]thio]}-1,3,4-
oxadiazole (
8a-n) were synthesized by stirring 5 and N-aryl-2-bromoacetamides (
7a-n) in an aprotic
polar solvent. The structures were corroborated by infrared (IR), electron impact mass spectrometry (EI-MS)
and proton/carbon nuclear magnetic resonance (
1H/
13C-NMR) spectroscopic techniques. The
evaluation of antibacterial activity was based on the effect on the increase in absorbance of the broth
medium due to log phase microbial growth.
Results: Compound
8g bearing a 2-methylphenyl group was the most the active growth inhibitor of
Salmonella typhi
,
Escherichia coli
,
Pseudomonas aeruginosa
,
Staphylococcus aureus
and
Bacillus subtilis
bacterial strains with minimum inhibitory concentrations (MIC) of 10.63±0.97, 10.31±1.00, 10.45
± 0.94 and 11.77±5.00 μM, respectively. Ciprofloxacin was used as reference standard.
Conclusion: All the synthesized compounds are moderate inhibitors but relatively more active against
Gram-negative bacterial strains. 5-{1-[(4-Chlorophenyl)sulfonyl]piperidin-4-yl}-2-{[N-(2-methylphenyl)-2-acetamoyl]thio]}-1,3,4-oxadiazole (
8g) is the most active growth inhibitor of all the strains except
Staphylococcus aureus.