Cryptobrachytone C from Cryptocarya pulchrinervia (Kosterm) Leaves on Proliferation, Apoptosis, Migration and Clonogenicity of MCF-7 and T47D Cell Lines.

Cryptocarya pulchrinervia is an Indonesian indigenous plant that grows in Sumatra, Kalimantan and Papua. One of the new compounds extracted from this plant was cryptobrachytone C, which was known to be cytotoxic against cancer cells of Murine leukemia P388 with IC50 10.52 µM. In this study, the cytotoxicity and anticancer properties of cryptobrachytone C on proliferation, apoptosis, migration and clone formation of MCF-7 and T47D breast cancer cell lines were examined, which had not previously been done before. The cytotoxicity of the compound was measured using an MTT (3- (4,5-dimethylthiazol-2- yl) -2,5-di-phenyl-tetrazolium bromide) assay. The cell proliferation was measured using a BrdU assay, and the cell apoptosis was measured using annexin-V FITC, while the cell migration was measured using a transwell filter. The cytotoxic test result demonstrated that cryptobrachytone C was cytotoxic against MCF-7 cells with IC50 12.94 ± 0.32 µM but not against T47D cells with IC50 65.33 ± 2.33 µM nor against normal MRC-5 cells with IC50 122.57 ± 19.84 µM. The cell proliferation assay showed that cryptobrachytone C at IC50 concentration had antiproliferative properties against MCF-7 cancer cell lines (p < 0.05) but did not significantly reduce T47D cell proliferation (p < 0.07). Although the results of the cell apoptosis test showed that cryptobrachytone C could induce the apoptosis of the MCF-7 and T47D cells, it was insignificant (p > 0.05). The cell migration test showed that cryptobrachytone at IC50 concentrations could inhibit the migration of the MCF-7 and T47D cells. The clonogenic test showed that cryptobrachytone C at IC50 concentration can induce the inhibition of the formation of MCF-7 and T47D cell colonies. The cryptobrachytone C anti-cancer character was more signi icant on the MCF-7 cell line compared to the T47D. This study showed that cryptobrachytone C was cytotoxic and had potential as an anti-cancer compound against MCF-7 and T47D breast cancer cell lines.

Cinnamoyl Dipyrromethenes as Fluorescence Zinc(II) Ion Sensor.

Friedel-Crafts acylation of dipyrromethane with cinnamoyl chloride was conducted to obtain dicinnamoyl dipyrromethane compounds 3 and 4. Both compounds were subsequently oxidized by DDQ to produce dicinnamoyl dipyrromethene ligands (DC-1 and DC-2). A large bathochromic shift compared to dipyromethene (D) was observed at 95 nm for DC-1 and 67 nm for DC-2. Both compounds showed remarkable chelation-enhanced fluorescence (CHEF) upon addition of zinc(II) ions. Similar to the quadrupolar system, DC-1 exhibited absorption and emission near the optical windows of the tissue. However, asymmetrical DC-2 had a better "turn-on" CHEF, with a fluorescence intensity that was 22 times higher than that of compound D. The DC-2 ligand also showed a limit of detection (LOD) of up to 3.0×10-8  M and selectivity toward zinc(II) ions compared to alkali and alkaline earth metal ions.

Secorubenine, a Monoterpenoid Indole Alkaloid Glycoside from Adina rubescens: Isolation, Structure Elucidation, and Enantioselective Total Synthesis.

A new pentacyclic monoterpenoid indole alkaloid glycoside named secorubenine (1) was isolated from the heartwood of Adina rubescens, collected in Indonesia. The structure was elucidated by spectroscopic analysis and chemical modification of isolated secorubenine (1). The bioinspired enantioselective total synthesis of 1 was accomplished in 12 steps, whereafter its structure was determined and the absolute stereochemistry was confirmed.

Naturally occurring biflavonoids with amyloid ß aggregation inhibitory activity for development of anti-Alzheimer agents.

Amyloid ß (Aß) aggregation plays an essential role in promoting the progression of Alzheimer's disease (AD). Therefore, the inhibition of Aß aggregation is a potential therapeutic approach for AD. Herein, twenty-seven biflavonoids with different inter-flavonyl linkages and methoxy substitution patterns were isolated from several plants, and their Aß40 aggregation inhibitory activity was evaluated by the thioflavin-T fluorescence assay. Amentoflavone (1) and its monomethoxy derivatives (2, 3, and 5) exhibited the most potent inhibitory activity, with IC50 values of approximately 5 µM. It was clarified that increasing the number of methoxy substituents on the biflavonoid structures attenuated the inhibitory activity. Moreover, the linkage and the methoxy substitution pattern had a marked influence on the inhibitory activity. Our investigation strongly supports that biflavonoids can be considered a new type of anti-Alzheimer agents that may be successfully developed for AD patients.

Anti-angiogenic effect of α-mangostin.

Eleven known prenyl xanthones, isolated from the pericarp of Garcinia mangostana, were tested for their ability to inhibit the phosphorylation of kinase domain receptor (KDR) tyrosine kinase. α-Mangostin was found to inhibit phosphorylation of KDR. α-Mangostin also showed to inhibit phosphorylation of the Y1175 residue of KDR (10 µM). This is the first report that α-mangostin inhibited the phosphorylation of KDR tyrosine kinase and also the Y1175 residue of KDR. α-Mangostin also showed inhibitory effects on proliferation of human umbilical vein endothelial cells (HUVECs) (IC(50) 1.2 µM) and human umbilical artery endothelial cells (IC(50) 2.4 µM), as well as the migration (IC(50) 0.034 µM) and tubule formation (at the concentrations of 0.6 and 1.2 µM) of HUVECs. These results suggest that the inhibition of the phosphorylation of KDR tyrosine kinase is concerned in the anti-angiogenic activity of α-mangostin.