Synthesis of N-substituted acetamide derivatives of azinane-bearing 1,3,4-oxadiazole nucleus and screening for antibacterial activity

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

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, 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.