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

• Published in: Tropical Journal of Pharmaceutical Research
• Main Author: Iqbal K.; Jamal Q.; Iqbal J.; Afreen M.S.; Sandhu M.Z.A.; Dar E.; Farooq U.; Mushtaq M.F.; Arshad N.; Iqbal M.M.
• Format: Article
• Language: English
• Published: University of Benin 2017
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014071417&doi=10.4314%2ftjpr.v16i2.23&partnerID=40&md5=3d91028fd6009850829ed0fe1d2c84f5

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 (EIMS) 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. © Pharmacotherapy Group, Faculty of Pharmacy, 2017. All rights reserved.