Antiproliferative piperidine alkaloids from giant taro (Alocasia macrorrhiza) / 中国天然药物

The rhizome of giant taro (Alocasia macrorrhiza (L.) Schott), which is a highly adaptable wild plant, is a traditional Chinese herbal medicine. In the current study, the antiproliferative constituents of giant taro were investigated and six new (1-6) and four known piperidine alkaloids (7-10) were isolated from its rhizomes. Their chemical structures and absolute configurations were elucidated using various spectroscopic methods and the Mosher ester method. The isolated alkaloids were screened for the antiproliferative activity through MTT assay. The results indicated that piperidine alkaloids exerted potential antiproliferative activity against HepG2, AGS and MCF-7 tumor cells. Further researches showed that compounds 3-5 dose-dependently decreased the colony formation rate and induced the apoptosis of AGS cells, while compound 4 induced AGS cell death via the proapoptotic pathway. This study demonstrates that the piperidine alkaloids isolated from giant taro exhibit significant antitumor activity, which provides phytochemical evidence for further development and utilization.

Characterization and cytotoxic activity on glial cells of alkaloid-enriched extracts from pods of the plants Prosopis flexuosa and Prosopis nigra (Fabaceae) / Caracterización, y actividad citotóxica en células gliales, de extractos enriquecidos con alcaloides de vainas de las plantas Prosopis flexuosa y Prosopis nigra (Fabaceae)

Introduction: Prosopis spp. pods have shown to be a potential source of protein and energy in livestock. However, prolonged ingestion of some of these species produces neurological symptoms in ruminants. Objective: In the present study, the alkaloid content and the in vitro neurotoxic activity of alkaloid enriched-extracts from P. flexuosa and P. nigra pods were determined in order to elucidate the mechanism of animal poisoning caused by these species. Methods: The main alkaloids present in both extracts were analysed by high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS). The cytotoxic activity of Prosopis alkaloid enriched-extracts in primary mixed glial cell culture was assessed by phase contrast microscopy and using neutral red, and lactate dehydrogenase (LDH) activity assays. Results: Juliprosine and juliprosopine were identified in P. flexuosa pods, while the absence of these alkaloids in P. nigra was confirmed. Both extracts (5-30 μg/mL) induced in a dose dependent manner, morphological alterations, such as swelling, enlargement and detachment from the culture surface. Consistent with this, decrease in cell viability and release of LDH 48 hours after exposure, revealed that P. flexuosa pods was significantly more cytotoxic than P. nigra. Conclusions: In P. flexuosa pods, juliprosine and juliprosopine alkaloids were identified for the first time. Moreover, the present study suggests that the cytotoxic effect displayed by both extracts is due to its alkaloid content. However, the presence of piperidine alkaloids in P. flexuosa could explain the greater cytotoxicity on glial cells with respect to P. nigra that was not shown to contain these alkaloids.

Introducción: Las vainas de diversas especies de Prosopis muestran ser una potencial fuente de proteínas y energía para el ganado. Sin embargo, la ingestión prolongada de algunas de estas especies produce síntomas neurológicos en los rumiantes. Objetivo: En el presente estudio se determinó el contenido de alcaloides y la actividad neurotóxica in vitro de los extractos enriquecidos con alcaloides obtenidos en las vainas de P. flexuosa y P. nigra, con el fin de dilucidar el mecanismo de la intoxicación animal causada por estas especies. Métodos: Los principales alcaloides presentes en ambos extractos se analizaron mediante cromatografía líquida de alto rendimiento-espectrometría de masas de alta resolución (HPLC-HRMS). La actividad citotóxica de los extractos enriquecidos con alcaloides de Prosopis se determinó en cultivos primarios de células gliales mixtas y se evaluó mediante microscopía de contraste de fase y utilizando ensayos de actividad de rojo neutro y de deshidrogenasa láctica (LDH). Resultados: Se identificaron la juliprosina y la juliprosopina en las vainas de P. flexuosa, mientras que se confirmó la ausencia de estos alcaloides piperidínicos en P. nigra. Ambos extractos (5-30 μg/mL) indujeron, de manera dependiente a la dosis, alteraciones morfológicas, como hinchazón, agrandamiento y desprendimiento de la superficie de cultivo. En consecuencia, la disminución de la viabilidad celular y la liberación de la LDH después de 48 horas de exposición, reveló que las vainas de P. flexuosa eran significativamente más citotóxicas que las de P. nigra. Conclusiones: El presente estudio muestra la presencia de los alcaloides juliprosina y juliprosopina en vainas de P. flexuosa y sugiere que el efecto citotóxico mostrado por ambos extractos se debe al contenido de alcaloides. Sin embargo, la presencia de estos alcaloides piperidínicos en P. flexuosa podría explicar la mayor citotoxicidad en las células gliales con respecto a P. nigra que no mostró que tuviera estos alcaloides.

Biological activity of synthesized 5-{1-[(4-chlorophenyl)sulfonyl]piperidin-4-yl}-2-mercapto-1, 3, 4-oxadiazole derivatives demonstrated by in silico and BSA binding studies

We synthesized a series of compounds bearing pharmacologically important 1,3,4-oxadiazole and piperidine moieties. Spectral data analysis by 1H-NMR, 13C-NMR, IR and EI-MS was used to elucidate the structures of the synthesized molecules. Docking studies explained the different types of interaction of the compounds with amino acids, while bovine serum albumin (BSA) binding interactions showed their pharmacological effectiveness. Antibacterial screening of these compounds demonstrated moderate to strong activity against Salmonella typhi and Bacillus subtilis but only weak to moderate activity against the other three bacterial strains tested. Seven compounds were the most active members as acetyl cholinesterase inhibitors. All the compounds presented displayed strong inhibitory activity against urease. Compounds 7l, 7m, 7n, 7o, 7p, 7r, 7u, 7v, 7x and 7v were highly active, with respective IC50 values of 2.14±0.003, 0.63±0.001, 2.17±0.006, 1.13±0.003, 1.21±0.005, 6.28±0.003, 2.39±0.005, 2.15±0.002, 2.26±0.003 and 2.14±0.002 µM, compared to thiourea, used as the reference standard (IC50 = 21.25±0.15 µM). These new urease inhibitors could replace existing drugs after their evaluation in comprehensive in vivo studies.

Effect of Prosopis ruscifolia on lipid profile in alloxan-induced hyperglycemic mice and chemical characterization of alkaloid and flavonoid fractions

Diabetes mellitus interferes with the metabolism of carbohydrates, causing chronic hyperglycemia. Dyslipidemiain diabetes is a condition that leads to cardiovascular disease. This study was aimed to evaluate the effect of hydroalcoholic Prosopis ruscifolia (Pr) leaves extract on hyperglycemia and lipid profile in normo- and hyperglycemicmice. Mice hyperglycemia was induced by alloxan, animals were treated with Pr (50, 100, 200 mg/kg, p.o., 28 days).Fasted blood glucose level on days 7, 14, 21, and 28 was determined. Blood glucose remained within the normalrange in the groups of normoglycemic animals treated with Pr. In the hyperglycemic animals, 100 mg/kg of Pr extractreduced the glycemia, this effect became markedly evident since day 7, until the end of experimental period (p <0.0001), the total reduction reached was 60%. The lipid profile of normal and hyperglycemic mice was evaluated with100 mg/kg, on day 28. A non-significant increase in total cholesterol and low density cholesterol, in hyperglycemicanimals treated with vehicle, and a statistically significant increase (p < 0.0001) in the level of triglyceride and verylow density cholesterol (VLDL) level (p < 0.0001) in normoglycemic animals treated with Pr, compared to the controlgroup were denoted. This could indicate that Pr has a stimulating action on insulin secretion, since hyperinsulinemiais also associated with an increase in the quantity of atherogenic particles of VLDL cholesterol and triglycerides.The coronary risk index and the atherogenic index of hyperglycemic animals treated with Pr showed a reductioncompared with the untreated hyperglycemic ones. The presence of three piperidine alkaloids, juliprosopine, 3’’’’–Oxo-juliprosopine, and julifloridine, previously isolated from P. juliflora, was confirmed. Also, the presence of theflavonoid quercetin was detected in this plant. Those compounds are strong candidates presumably responsible forimparting the effect on glycemia and lipid profile reported here.

Autophagy protects against neural cell death induced by piperidine alkaloids present in Prosopis juliflora (Mesquite)

ABSTRACT Prosopis juliflora is a shrub that has been used to feed animals and humans. However, a synergistic action of piperidine alkaloids has been suggested to be responsible for neurotoxic damage observed in animals. We investigated the involvement of programmed cell death (PCD) and autophagy on the mechanism of cell death induced by a total extract (TAE) of alkaloids and fraction (F32) from P. juliflora leaves composed majoritary of juliprosopine in a model of neuron/glial cell co-culture. We saw that TAE (30 µg/mL) and F32 (7.5 µg/mL) induced reduction in ATP levels and changes in mitochondrial membrane potential at 12 h exposure. Moreover, TAE and F32 induced caspase-9 activation, nuclear condensation and neuronal death at 16 h exposure. After 4 h, they induced autophagy characterized by decreases of P62 protein level, increase of LC3II expression and increase in number of GFP-LC3 cells. Interestingly, we demonstrated that inhibition of autophagy by bafilomycin and vinblastine increased the cell death induced by TAE and autophagy induced by serum deprivation and rapamycin reduced cell death induced by F32 at 24 h. These results indicate that the mechanism neural cell death induced by these alkaloids involves PCD via caspase-9 activation and autophagy, which seems to be an important protective mechanism.

Piperidine alkaloids from Lobelia polyphylla Hook. & Arn. (Campanulaceae) / Alcaloides piperidínicos de Lobelia polyphylla Hook. & Arn. (Campanulaceae)

The piperidine alkaloid composition from young stems of Lobelia polyphylla Hook & Arn. was determined by gas chromatography mass spectrometry (GC-MS). The tentative structures, without the stereochemistry, were obtained by the analysis of the fragmentation patterns of the mass spectra of each compound. The stems contained a mixture of lobeline (1), norlobelanidine (2), 1-(1-(2-hydroxy-2-phenylethyl)-1-methylpiperidin) butane-2-ol (3), 8-propyl-10-phenyl lobelionol (4), 1-(6-(2-hydroxy-2-phenylethyl)-1-methylpiperidin) butane-2-one (5), 1-(6-(2-hidroxypentyl)-1-ethylpiperidin) butane-2-one (6) and 1-methyl-2-piperidinemethanol (7). The role of these alkaloids in the toxic, narcotic and hallucinogenic effects, produced after smoking the aerial parts of this species is discussed.

La composición de alcaloides piperidínicos de tallos jóvenes de Lobelia polyphylla Hook & Arn. se determinó por cromatografía de gases acoplada a espectrometría de masas (CG-EM). Las estructuras tentativas sin incluir la estereoquímica, se obtuvieron mediante el análisis de los patrones de fragmentación de los espectros de masas de cada compuesto. Los tallos contienen una mezcla de lobelina (1), norlobelanidina (2), 1-(1-(2-hidroxi-2-feniletil)-1-metilpiperidin) butano-2-ol (3), 8-propil-10-fenil lobelionol (4), 1-(6-(2-hidroxi-2-feniletil)-1-metilpiperidin) butano-2-ona (5), 1-(6-(2-hidroxypentyl)-1-etilpiperidin) butano-2-ona (6) y 1-metil-2-piperidinmetanol (7). Se discute el posible papel de estos alcaloides en los efectos tóxicos, estupefacientes y alucinógenos, producidos después de haber fumado la parte aérea de esta especie.

Synthesis and antimicrobial study of N-[4-(2-piperidine-1-yl-ethoxy) phenyl] acetamide analogues.

In the present study, a novel series of N-[4-(2-piperidine-1-yl-ethoxy) phenyl]- acetamides were synthesized from 4-aminophenol and characterised by IR, 1H-NMR, Mass spectral studies and elemental analysis. The antimicrobial potency of compounds is tested against variety of fungal and bacterial strains by disc agar diffusion technique. in comparison to to fluconazole and chloramphenicol respectively. Some of the synthesized compounds exhibit the potency comparable to that of standard drugs.

Comparison remifentanil and fentanyl in combined anesthesia of gynaecologic laparoscopy / 重庆医科大学学报

Objective:The purpose of this study is to evaluate the clinical efficacy of remifentanil combined with proopofol in the course of anesthesia induction and analepsia. Methods: 90 ASAⅠ～Ⅱpatients excision of tumor of the ovary and salphingectomy undergoing gynaecologic laparoscopy were randomly divided into two groups:R group (propofol and vemifentanil n=45) and F group (propofol and fentanil n=45).MAP and HR were observed at the time of anesthesia induction tracheal intubation;the time of spontaneuusly breathing,awakeness,extubation,orientation force and the time of PACU were record;we view the patient of conscious state,cognition functional and the degree of pain;and observe the side effects of nausea and vomitting,intraoperative awareness and degree of patients'satisfaction. Result:There was no significant diference in decrease of two group of MAP in the course of anesthesia. The rate of cardiovascular response to tracheal intubation in F group is higher than that in R group, and hemobynamics was stabler. There was significantly diference in the time of spontaneously breathing,awakeness and extubation. At the time instant extubation and departing PACU were shorter, VAS after extubation 1h in R group was higher than that in F group. There was no significant diference in incidence rate of postoperative nausea and vomitting. Conclusion: Awake qualily of intravenous anesthesia with Propofol and remifentanil was better than that with Propofol and fentanil in excision of tumor of the ovary and salpingectomy undergoing gynaecologic laparoscopy. As half life of remifentanil was short, patients felt pain soon after operation and pestoperative analgesia should be performed promptly.

Synthesis and bioactivities of some cis-diamin complex of piperidine or morpholine and other amin containing platin (II)

Three complexes of cis-dichloro (piperdine) (amine) platinum (II) and there complexes of cis-dichloro (morpholine) (amine) platinum(II) including [Pt(Pip)(Pyridine)Cl2], {Pt(Pip)(o -{Pt(Pip)(o-Toluidine)Cl2] have been synthesized and characterized by elemental analysis< molar conductivity, IR and Raman spectral studies. The complexes were tested for biological activities and found to be capable of inhibiting the growth of some human cancer cells. This result showed that the presence of piperidine in prepared complexes influenced on their biological activities clearer than as compared to the complexes containing morpholine.

Isolamento biomonitorado de alcalóides tóxicos de Prosopis juliflora (algaroba) / Bioassay-guided isolation of toxic alkaloids of Prosopis juliflora (mesquite)

Uma investigação fitoquímica das vagens de Prosopis juliflora cultivada na região semi-árida do Estado da Paraíba e monitorada através de testes farmacológicos levou ao isolamento, purificação e identificação do alcalóide principal juliprosopina. A presença de outros constituintes químicos em mistura, tais como juliprosina e juliprosineno, foi verificada na fração dos alcalóides totais através de uma análise do espectro de RMN de 13C. Este trabalho sugere que a toxicidade, observada em animais de laboratório, está quimicamente relacionada com os alcalóides piperidínicos presentes nas vagens desta leguminosa.

A phytochemical investigation of the pods of Prosopis juliflora cultivated in the semi arid region of the State of Paraiba, monitored by pharmacological tests, led to the isolation, purification and identification of its main alkaloid - juliprosopine. The presence of other compounds such as juliprosine and juliprosinene, was observed through analysis of 13C NMR. This work suggests that the toxic activity, observed in laboratory animals, is chemicaly related with the piperidine alkaloids present in the pods of this Leguminosae.