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 (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.Keywords: 1,3,4-Oxadiazole, Acetamides, Antibacterial activity, Piperidin

VALIDATION OF HEPATOPROTECTIVE USE OF POLYGONUM PERFOLIATUM EXTRACT AGAINST PARACETAMOL INDUCED TOXICITY IN WISTAR RATS

The liver as a vital body organ is adversely affected by hazardous chemicals and drugs. Paracetamol widely used as analgesic and antipyretic drug produces severe hepatotoxicity at high doses. Present study was designed to investigate the hepatoprotective activity of Polygonum perfoliatum L. used on folklore basis. Aqueous methanolic extract of the plant was prepared. Preliminary phytochemical and HPLC analyses were carried out to identify and quantify chemical constituents respectively. For hepatoprotective activity, Wistar rats were divided into six groups as normal control, standard (silymarin) control, negative control and extract treated groups i.e., 125, 250 and 500 mg/kg/day per oral. Paracetamol was administered orally, following seven days of previously stated therapy. Biochemical parameters of hepatotoxicity such as serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP) and total bilirubin were measured in all groups. Histopathological evaluation of liver was also carried out. Benzoic acid, chlorogenic acid, gallic acid, m-coumaric acid, quercetin and vitamin E were detected in the plant extract through HPLC. The hepatoprotective effect of 500 mg/kg/day therapy was more pronounced than 125 and 250 mg/kg dose. However, the effect of plant extract was less pronounced than standard silymarin therapy. It can be concluded that the plant extract possessed significant hepatoprotective activity that may be attributed to quercetin, benzoic acid, gallic acid and vitamin E present in it