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[Display omitted] • Compound 2h is the most potent against A549 cells with the IC 50 value of 0.27 µM; • Compound 2h inhibits A549 proliferation and arrest A549 cells at G2/M cycle; • Compound 2h can influence A549 cell migration and invasion and induce cells apoptosis; • Compound 2h can inhibit the activation of PI3K/Akt/mTOR signaling pathway in vivo ; Fangchinoline (Fan) are extracted from the traditional Chinese medicine Stephania tetrandra S. , which is a bis-benzyl isoquinoline alkaloids with anti-tumor activity. Therefore, 25 novel Fan derivatives have been synthesized and evaluated for their anti-cancer activity. In CCK-8 assay, these fangchinoline derivatives displayed higher proliferation inhibitory activity on six tumor cell lines than the parental compound. Compared to the parent Fan, compound 2h presented the anticancer activity against most cancer cells, especially A549 cells, with an IC 50 value of 0.26 μM, which was 36.38-fold, and 10.61-fold more active than Fan and HCPT, respectively. Encouragingly, compound 2h showed low biotoxicity to the human normal epithelial cell BEAS-2b with an IC 50 value of 27.05 μM. The results indicated compound 2h remarkably inhibited the cell migration by decreasing MMP-2 and MMP-9 expression and inhibited the proliferation of A549 cells by arresting the G2/M cell cycle. Meanwhile, compound 2h could also induce A549 cell apoptosis by promoting endogenous pathways of mitochondrial regulation. In nude mice presented that the growth of tumor tissues was markedly inhibited by the consumption of compound 2h in a dose-dependent manner, and it was found that compound 2h could inhibit the mTOR/PI3K/AKT pathway in vivo. In docking analysis, high affinity interaction between 2h and PI3K was responsible for drastic kinase inhibition by the compound. To conclude, this derivative compound may be useful as a potent anti-cancer agent for treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Small berries have become an attractive topic of research due to their high content in phenolic compounds and reported antioxidant activity. However, there are currently few reports on the deep characterization of their polyphenol composition. Five kinds of berries (raspberry, blackberry, blueberry, mulberry and black chokeberry) were studied to compare the antioxidant activities and polyphenol compositions of both berry juice and pomace (by-products in processing). Results showed that pomaces were more potent antioxidants than juices, especially those that originated from red raspberry. The polyphenol contents in pomaces ranged from 137 to 222 mg/g, this was higher than juices that ranged from 2.75 to 8.88 mg/g, with mulberry accounting for the highest content. The main compounds in pomaces were phenolic compounds with different relative contents found by UPLC-MS/MS. A total of 568 compounds were identified, including 238 flavonoids and 131 phenolic acids. PCA, HCA and OPLS-DA analyses were performed to find similarities on the polyphenol and metabolomic profile of the sampled berries. This analysis unveiled that all studied berries presented a significantly different polyphenol profile, on which raspberry and blackberry were the most similar. Results suggested that berry pomaces can be valuable sources of phenolic compounds of which the major components are anthocyanins and phenolic acids, with potential applications as antioxidant food additives, or raw materials for pharmaceuticals, nutraceuticals, and cosmetics. [Display omitted] • The antioxidant and phenolic composition of berry juice and pomace was evaluated. • Pomaces had higher antioxidant activity than the juices, highlighting red raspberry. • Phenolics in pomaces ranged from 137 to 221 mg/g, and in juices ranged from 2.75 to 8.88 mg/g. • 238 flavonoids and 131 phenolic acids were identified in pomace samples. [ABSTRACT FROM AUTHOR]

To extend shelf-life and develop new bayberry products, the effects of storage time and temperature on polyphenolic content and qualitative characteristics of freeze-dried and spray-dried bayberry power were studied. Results showed that the retention of total polyphenols, gallic acid, protocatechuic acid, cyanidin-3-o-glucoside and anthocyanins in the freeze-dried bayberry powder was in most cases higher than in the spray-dried powder when they were stored for the same period. The content of these components in both the freeze-dried and spray-dried bayberry powder decreased gradually with the longer storage time. No significant difference was detected for the retention of these compounds whether they were stored at 4 °C or 25 °C. The browning index of both the freeze-dried and spray-dried powder significantly increased during a 50-day storage period. The ΔE value of the bayberry powder stored at 25 °C was distinctly higher than that of the other treated samples; a value of the spray-dried powder was slightly higher than that of the other samples. All presented results indicate that freeze-drying and 4 °C storage is an efficient and convenient method to maintain the bioactive polyphenolic components and high-qualitative characteristics of bayberry fruits. [ABSTRACT FROM AUTHOR]

Scheme 1. Synthesis of nuciferine derivative 1a-1r,2a-2l. Reagents and conditions: (a) 48% HBr solution, glacial acetic acid, 70 °C; (b) Et 3 N, N 2 , CH 2 Cl 2 , 25℃, 1h; (c) NaH, N 2 , DMF, 0 °C, 2h. [Display omitted] • The inhibition effect of compound 1j (104.46 ± 4.07%) was roughly the same as benzbromarone (101.44 ± 6.21%) in UA-induced HK-2 cells model; • Compound 1j inhibited the expression of URAT1 and GLUT9 through repressing PI3K/Akt pathway in HK-2 cells; • Compound 1j can promote the excretion of uric acid and thereby increase the fraction of uric acid excretion in vivo ; • Compound 1j can ameliorate renal inflammation and reduce the level of renal inflammatory factors; • Compound 1j shows nephroprotective effect through regulate TLR4/IκBα/NF-κB signaling pathway; Hyperuricemia is a common metabolic disease with a series of complications. Nuciferine, a typical aporphine alkaloid natural compound extracted from the leaves of Nelumbo nucifera Gaertn., was confirmed to have an antihyperuricemia effect. In the present study, 30 novel nuciferine derivatives were designed and synthesized. The effects of all derivatives on the regulation of URAT1 were studied in a uric acid-induced HK-2 cell model with benzbromarone as a positive control. The results indicated that Compound 1j showed the optimal URAT1 inhibitory activity through repressing PI3K/Akt pathway in HK-2 cells and the inhibitory effect was similar to that of benzbromarone. In addition, in vivo experiments demonstrated that Compound 1j could reduce uric acid levels and ameliorate kidney damage in hyperuricemic mice. On the one hand, Compound 1j could inhibit the expression of URAT1 and GLUT9 to increase the uric acid excretion index. On the other hand, Compound 1j could regulate the TLR4/IκBα/NF-κB signaling pathway to reduce the levels of inflammatory cytokines, thereby alleviating kidney damage. Meanwhile, a molecular docking assay revealed the potential molecular binding power (-9.79 kcal/mol) between Compound 1j and URAT1, which was more tightly bound than the lead compound nuciferine (-7.44 kcal/mol). Based on these results, Compound 1j may be a future drug for the development of new potential antihyperuricemia and nephroprotective drug candidates. [ABSTRACT FROM AUTHOR]

[Display omitted] • 10 of the 20 synthetic derivatives exhibited significant antitumor activity. • Compound 4g shows the most potent against A549 cells (14.34-fold of d- Tet). • Compound 4g inhibits A549 proliferation, migration, invasion and arrest G2/M cycle. • Compound 4g can induce apoptosis by inactivating the PI3K/Akt/mTOR pathway. Cancer treatment is one of the major public health issues in the world. Tetrandrine (Tet) and fangchinoline (d -Tet) are two bis -benzyl isoquinoline alkaloids extracted from Stephania tetrandra S. Moore, and their antitumor activities have been confirmed. However, the effective dose of Tet and d -Tet were much higher than that of the positive control and failed to meet clinical standards. Therefore, in this study, as a continuation of our previous work to study and develop high-efficiency and low-toxic anti-tumor lead compounds, twenty new Tet and d -Tet derivatives were designed, synthesized and evaluated as antitumor agents against six cancer cell lines (H460, H520, HeLa, HepG-2, MCF-7, SW480 cell lines) and BEAS-2B normal cells by CCK-8 analysis. Ten derivatives showed better cytotoxic effects than the parent fangchinoline, of which 4g showed the strongest cell growth inhibitory activity with an IC 50 value of 0.59 μM against A549 cells. Subsequently, the antitumor mechanism of 4g was studied by flow cytometry, Hoechst 33258, JC-1 staining, cell scratch, transwell migration, and Western blotting assays. These results showed that compound 4g could inhibit A549 cell proliferation by arresting the G2/M cell cycle and inhibiting cell migration and invasion by reducing MMP-2 and MMP-9 expression. Meanwhile, 4g could induce apoptosis of A549 cells through the intrinsic pathway regulated by mitochondria. In addition, compound 4g inhibited the phosphorylation of PI3K, Akt and mTOR, suggesting a correlation between blocking the PI3K/Akt/mTOR pathway and the above antitumor activities. These results suggest that compound 4g may be a future drug for the development of new potential drug candidates against lung cancer. [ABSTRACT FROM AUTHOR]

• Compound 3i was most effective against A549 cells with an IC 50 value of 0.61 µM. • Compound 3i is less toxic to normal human liver cells with an IC 50 value of 27.53 μM. • Compound 3i arrests A549 cells in the G2 / M phase to prevent their proliferation. • Compound 3i induced apoptosis in A549 cells via the mitochondrial pathway. • The study shows that compound 3i is an excellent anti-tumor potential drug candidate. The isolation and modification of natural products play an important role in the synthesis of anti-tumor drugs for the treatment of cancer. The present study was designed to evaluate the effects of fangchinoline derivatives against cancer cells. In vitro cytotoxicity of all derivatives against five cancer cell lines (A549, Hela, HepG-2, MCF-7 and MDA-MB-231 cell lines) and HL-7702 normal cells was assessed using the CCK-8 assay, and the results showed that most of the synthesized compounds displayed better cytotoxic effects on all the tested cells compared to that of the parent fangchinoline. In particular, compound 3i had the strongest inhibitory effect on cell proliferation, with an IC 50 value of 0.61 µM against A549 cells. Compared with fangchinoline and HCPT (hydroxycamptothecine), the anti-proliferative activity of compound 3i was significantly increased. More interestingly, compound 3i had slight toxic side effects on normal cells, with an IC 50 value of 27.53 µM. Moreover, the cell viability and cell cycle assays revealed that compound 3i inhibited A549 cell proliferation and arrested A549 cells at the G2/M-phase. The apoptosis-inducing effects of compound 3i and the associated molecular mechanisms were assessed using flow cytometry, cell staining, reactive oxygen species assays, RT-qPCR and Western blot analysis. These results suggested that compound 3i induces apoptosis through a mitochondria-mediated intrinsic pathway. This study revealed that compound 3i is a promising candidate for future development as an anti-tumor drug. [ABSTRACT FROM AUTHOR]