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Synthesis and antibacterial study of some s-substituted aliphatic analogues of 2-mercapto-5-(1-(4-toluenesulfonyl) piperidin-4-yl)-1,3,4-oxadiazole
Sattar, A; ur-Rehman, Aziz; Abbasi, MA; Siddiqi, SZ; Nafeesa, K & Ahmad, I
Abstract
Purpose: To synthesize a series of analogues of 1,3,4-oxadiazole and to evaluate their antibacterial
activity.
Methods: Ethyl piperidin-4-carboxylate (1) was mixed with 4-toluenesulfonyl chloride (2) in benignant
conditions to yield ethyl 1-(4-toluenesulfonyl)piperidin-4-carboxylate (3) and then 1-(4-
toluenesulfonyl)piperidin-4-carbohydrazide (4). Intermolecular cyclization of 4 into 2-mercapto-5-(1-(4-
toluenesulfonyl) piperidin-4-yl)-1,3,4-oxadiazole (5) was obtained on reflux with CS2 in the presence of
KOH. Molecule 5 was stirred with alkyl halides, 6a-i, in DMF in the presence of LiH to synthesize the
final compounds, 7a-i. The structures of these molecules were elucidated by Fourier transform infra-red
(FTIR) spectroscopy, proton nuclear magnetic resonance (1H-NMR) and electron impact mass
spectrometry (EI-MS). Antibacterial activity was evaluated against five bacterial strains, namely,
Salmonella typhi, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus
subtilis, with ciprofloxacin used as standard antibacterial agent.
Results: Out of nine synthesized derivatives, compound 7a was the most active against three bacterial
strains, S. typhi, E. coli and P. aeruginosa, with minimum inhibitory concentration (MIC) of 9.11 ± 0.40,
9.89 ± 0.45 and 9.14 ± 0.72 μM, respectively, compared with 7.45 ± 0.58, 7.16 ± 0.58 and 7.14 ± 0.18
μM, respectively, for the reference standard (ciprofloxacin). Similarly, compounds 7a - 7c showed
relatively good antibacterial activity against B. subtilis strain while compound 7e - 7g revealed good
results against S. typhi bacterial strain.
Conclusion: The results indicate that S-substituted derivatives of the parent compound are more
effective antibacterial agents than the parent compound, even with minor differences in substituents
Keywords
1,3,4-Oxadiazole; Antibacterial activity; Ethyl piperidin-4-carboxylate; Sulfonamide
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