Synthesis of some novel enzyme inhibitors and antibacterial agents derived from 5-(1-(4-tosyl)piperidin-4-yl)-1, 3, 4-oxadiazol-2-thiol

ABSTRACT Keeping in mind the pharmacological importance of the 1,3,4-oxadiazole moiety, a series of new S-substituted derivatives, 5a-h, of 5-(1-(4-tosyl)piperidin-4-yl)-1,3,4-oxadiazol-2-thiol (3) were synthesized. The reaction of p-toluenesulfonyl chloride (a) and ethyl isonipecotate (b) produced ethyl 1-(4-tosyl)piperidin-4-carboxylate (1) which was further transformed into 1-(4-tosyl)piperidin-4-carbohydrazide (2) by hydrazine hydrate in methanol. Compound 2 was refluxed with CS2 in the presence of KOH to synthesize 5-(1-(4-tosyl)piperidin-4-yl)-1,3,4-oxadiazol-2-thiol (3). The desired compounds, 5a-h, were synthesized by stirring 3 with aralkyl halides, 4a-h, in DMF using NaH as an activator. The structures of synthesized compounds were elucidated by 1H-NMR, IR and EI-MS spectral studies. These compounds were further evaluated for enzyme inhibitory activity against lipoxygenase and alpha-glucosidase, along with antibacterial activity against Gram-negative and Gram-positive bacteria.

RESUMO Tendo em vista a importância farmacológica da porção 1,3,4-oxadiazol, sintetizou-se uma série de novos derivados S-substituídos, 5a-h, de 5-(1-(4-tosi)piperidin-4-il)-1,3,4-oxadiazol-2-tiol (3). A reação do cloreto de p-toluenossulfonila (a), com isonipecotato de (b) etila forneceu 1-(4-tosil)piperidin-4-carboxilato de metila (1), que foi, em seguida, transformado em 1-(4-tosil)piperidin-4-carbo-hidrazida (2) por reação com hidrato de hidrazina em metanol. O composto 2 foi submetido a refluxo com CS2 na presença de KOH para se obter 5-(1-(4-tosil)piperidin-4-il)-1,3,4-oxadiazol-2-tiol (3). Os compostos desejados, 5a-h, foram obtidos por agitação de 3 com haletos de aralquila, 4a-h, em DMF, na presença de NaH. As estruturas dos compostos sintetizados foram elucidadas através de análise dos espectros de 1H-MNR, IR e EI-MS. Estes compostos foram, ainda, avaliados quanto à inibição das enzimas lipoxigenase e alfa-glucosidase, juntamente com a atividade antibacteriana contra bactérias Gram positivas e Gram negativas.

Biological activities of polyphenols from Polygonum lapathifolium / Actividades biológicas de polifenoles de Polygonum lapathifolium

Polygonum lapathifolium is an invasive plant spread worldwide, which has been used in traditional medicine for its biological activities. We studied chemical profile of the aerial part using HPLC/DAD/ESI-MS. Eight flavonoids, two chalcones and gallic acid were isolated, identified nad tested for their activity in seven experimental models (for antioxidant, alpha/beta-glucosidase inhibitory, antimicrobial, anticholineserase activity). Our results showed that P. lapathifolium is a valuable source of compounds with perspective biological activities...

Polygonum lapathifolium es una planta invasora cuya presencia se extiende por todo el mundo y que ha sido utilizada en la medicina tradicional por sus actividades biológicas. Analizamos el perfil químico de la parte superficial utilizando HPLC/DAD/ESI-MS. Ocho flavonoides, dos chalconas y ácido gálico fueron aislados, identificados y analizados en relación a sus actividades en siete modelos experimentales (de actividad antioxidante, alfa/beta-glucosidasa inhibitoria, antimicrobiana, anticholineserasa). Nuestros resultados demuestran que P. lapathifolium es una valiosa fuente de compuestos con actividades biológicas prometedoras...

Production of enzymatic hydrolysate of Acetes chinensis with angiotensin Ⅰ -converting enzyme inhibitory and its antihypertensive effects on spontaneously hypertensive rats / 中国生化药物杂志

Purpose To produce enzymatic hydolysates with angiotensin Ⅰ-converting enzyme (ACE) inhibitory activity and antihypertensive activity from Acetes chinensis. Methods ACE inhibitory activity of the hydrolysates of Acetes chinensis by five commercial proteases were determined in vitro to select a protease as the enzyme used in the preparation of enzymatic hydrolysate of Acetes chinensis, and orthogonal trials were employed to optimize its hydrolysis parameters, spontaneously hypertensive rats (SHR) were used to assess in vivo the hypotensive effects of hydrolysate under optimized condition. Results The hydrolysate with IC50 being0.65 mg/ml was obtained under the optimized condition of pH 2.4, 41℃, 3 h hydrolysis time, 3% enzyme/substrate ratio (E/S) and 8 % substrate concentration, and a recorded SBP reduction of 3 886.3 Pa (29mmHg) at 4 h after administration (1.0 g/kg BW) was observed. Conclusion Peptic hydrolysate of Acetes chinensis shows significant ACE inhibitory activity and antihypertensive activity.

STUDY ON ANGIOTENSIN CONVERTING ENZYME INHIBITORY PEPTIDES FROM DIGESTION OF SOY PROTEIN IN VITRO / 营养学报

Objective: To investigate if angiotensin converting enzyme inhilitory(ACEI) peptides would be produced from SPI digested by a batch digestion system using enzymes similar to digestive enzymes in humans.Method: Simulate the conditions of human gastrointestinal digestion in a model digestion system in vitro and produce soy peptides from SPI digested using pepsin and pancreatin.In addition to monitoring ACEI activity in the total soy protein digest,the possibility of generating soy peptide fractions with more potent activity than the unfractionated digest was investigated by measuring activity of fractions obtained after ultrafitration,anion exchange,and RP-HPLC.Results: The generation of ACEI activity in SPI was determined after sequential digestion with pepsin and pancreatin.The inhibitory activity was highest within the first 20 min at pepsin digestion and decreased upon subsequent digestion with pancreatin.An IC50 value of 0.28?0.06 mg/ml was determined after 180 min of digestion,while no ACEI activity was measured for the undigested SPI at 0.73 mg/ml.Chromatographic fractionation of the SPI digest resulted in IC50 values of active fractions ranging from 0.13?0.03 to 0.93?0.08 mg/ml.Conclusion: Many different peptides with ACEI activities were produced after pepsin-pancreatin digestion of SPI in vitro and lead to the speculation that physiological gastrointestinal digestion could also yield ACE inhibitory peptides from SPI.