Piperidine Alkaloids with Diverse Skeletons from Anacyclus pyrethrum.

Fifteen new piperidine derivatives, pyracyclumines A-J (1-10), including five pairs of enantiomers, (+)-1/(-)-1 to (+)-5/(-)-5, together with three known compounds, agrocybenine (11), 4,6,6-trimethyl-5,6-dihydro-2(1 H)-pyridone (12), and 3,5,5-trimethyl-1,5-dihydro-2 H-pyrrol-2-one (13), were isolated from the roots of Anacyclus pyrethrum. Pyracyclumines A, B, and H (1, 2, and 8) possess a novel 6/5/6/6 dimeric piperidine skeleton, a unique 6/5/6 dimeric piperidine skeleton, and a 1,4,6-triazaindan skeleton, respectively. Pyracyclumine C (3) is based on a rare cyclopentane-piperidine framework. The structures of the isolated compounds were established by analysis of their NMR and HRESIMS data. The racemic pyracyclumines A-E (1-5) were further separated by chiral HPLC to give the enantiomers (+)-1/(-)-1 to (+)-5/(-)-5, for which the absolute configurations were determined by comparison of their experimental and calculated ECD spectra. The plausible biogenetic pathways of these piperidine alkaloids were proposed starting from the basic units of compounds 12 and 13. All of the isolated compounds were tested for their inhibitory effects on menin-mixed lineage leukemia 1 protein-protein interaction.

Highly conjugated norditerpenoid and pyrroloquinoline alkaloids with potent PTP1B inhibitory activity from Nigella glandulifera.

Three norditerpenoid alkaloids, nigelladines A-C (1-3), and one pyrroloquinoline alkaloid, nigellaquinomine (4), all possessing new skeletons with highly conjugated systems, were isolated from Nigella glandulifera. The 8aS-configuration for 1 and 2 was determined by comparison of the experimental and calculated electronic circular dichroism spectra. These alkaloids exhibited potent protein tyrosine phosphatase 1B (PTP1B) inhibitory activity but are devoid of cytotoxicity against the A431 cell line at 100 µM.

Optimal extent of lymphadenectomy improves prognosis and guides adjuvant chemotherapy in esophageal cancer: A propensity score-matched analysis.

BACKGROUND: The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma (ESCC) patients remained debatable. AIM: To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery. METHODS: In this retrospective, propensity score-matched study, we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019. Patients who underwent neoadjuvant therapy were excluded. We collected patients' clinicopathological features and information regarding lymph nodes, including the total number of resected lymph nodes (NRLN), and pathologically diagnosed positive lymph nodes (RPLN). SPSS and R software were used for statistical analysis. RESULTS: Among the included 1042 patients, two cohorts: ≤ 21 (n = 664) and > 21 NRLN (n = 378) were identified. The final prognostic model included four variables: T stage, N, venous thrombus, and the number of removed lymph nodes. Among them, NRLN > 21 was determined as an independent prognosticator after surgery for esophageal cancer (hazards regression = 0.66, 95% confidence interval: 0.50-0.87, P = 0.004). A nomogram was created based on the regression coefficients of the variables in the final model. In the training cohort, the predictive model displayed an uncorrected five-year overall survival C-index of 0.659, with a bootstrap-corrected C-index of 0.654. In the subgroup analysis, adjuvant chemotherapy was beneficial in the subgroup with NRLN > 21 and RPLN ≤ 0.16 and NRLN ≤ 21 and RPLN > 0.16. CONCLUSION: NRLN > 21 was an independent prognostic factor after ESCC surgery. The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

Biosorption of Cd(II) from aqueous solution by Pseudomonas plecoglossicida: kinetics and mechanism.

In our present study, we investigated the mechanism of Cd(II) biosorption from aqueous solution by Pseudomonas plecoglossicida using different instrumental techniques. The adsorption kinetics fitted well with the pseudo second-order model, suggesting that the Cd(II) adsorption by P. plecoglossicida consisted of a chemisorption and a physisorption process. Compared with the dead P. plecoglossicida cells, the live cells demonstrated the same adsorption capacity of Cd(II). Scanning electron microscope with energy dispersive X-ray spectroscopy analysis revealed that the main mechanism of adsorption was the combination of Cd(II) with the organic functional groups in the cell wall of P. plecoglossicida. Furthermore, Fourier transform infrared spectroscopic analysis of the metal-loaded biosorbent confirmed the participation of -NH, -OH, -CH, and -CONH groups in the uptake of Cd(II). Moreover, cation transport test revealed that ionic exchange interactions were involved in the Cd(II) adsorption. However, it only played a minor role in the Cd(II) biosorption process.

Alkaloid constituents from Viola tianschanica.

Eighteen previously undescribed alkaloids, tishaviolamines A-J, including eight pairs of enantiomers, together with two known benzylisoquinoline alkaloids, (-)-bicuculline and (-)-corlumine, were isolated from Viola tianschanica. Among them, tishaviolamine A-E were demonstrated to possess three types of unpresented skeletons. The structures of these alkaloids were established by comprehensive analyses of the 1D, 2D-NMR and (+)HRESIMS data. The absolute configurations of enantiomers were determined by comparing their calculated ECD spectra with the experimental ones. The menin-mixed lineage leukemia 1 protein-protein interaction inhibitory effect of the isolated compounds were also measured.

Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/Akt signaling pathway.

Diabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A-C (compounds A-C), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro. In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A-C. Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A-C. The results suggested that compounds A-C improved glucose metabolism through promoting synthesis of glycogen. Expression of PTP1B protein was inhibited by compounds A-C in L6 moytubes. PI3K-dependent Akt phosphorylation was found to be activated by compounds A-C and completely blocked by wortmannin (a PI3K inhibitor). Moreover, the insulin-mediated induction of insulin receptor substrate-1 (IRS-1) and glycogen synthase kinase-3ß (GSK-3ß) were also suppressed by wortmannin. Western blot results indicated that compounds A-C-induced IRS-1/Akt activation was likely a consequence of PTP1B inhibition. Compounds A-C promoted glycogen synthesis through Akt-mediated GSK3 phosphorylation. Therefore, activation of PI3K/Akt insulin signaling pathway and suppression of PTP1B is the molecular mechanism that contributes to the anti-diabetic effect of compounds A-C in cellular models. The three alkaloids potentially serve as lead compounds for the development of antidiabetic drugs.

Diterpenoid constituents of Euphorbia macrorrhiza.

Ten diterpenoids, named macrorilone A-B, macroripremyrsinone A, macrorilathyrone A-B, macrorieuphorone A-B and macroricasbalone A-C, together with ten known diterpenoids, jatrophalone, sikkimenoids A-D, jatrophodione A, latilagascenes F, jolkinol B, 15ß-O-benzoyl-5α-hydroxyisolathyrol and jatrophalactone were isolated from the whole plant of Euphorbia macrorrhiza C.A. Mey. These diterpenoids belong to six skeleton-types, including jatropholane, premyrsinane, lathyrane, euphoractin, casbene and rhamnofolane diterpenoids. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HRESIMS spectroscopic data. The absolute configurations of macrorilone B, macroripremyrsinone A and macrorilathyrone A were established by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. Several of the isolated compounds exhibited weak cytotoxicity against the KB and KBv200 cell lines with IC50 values ranging from 21.19 to 47.87µM. Some also showed multidrug resistance (MDR) reversal activity, among which macrorilathyrone B exhibited a remarkable inhibitory effect on P-gp-mediated drug exclusion.