Ying-Tong Di

Three New Indole Alkaloids from Trigonostemon lii

Three unprecedented indole alkaloids, trigonoliimines A-C (1-3) with a unique polycyclic system, were isolated from the leaves of Trigonostemon lii Y. T. Chang. The structures of 1-3 were determined by the spectroscopic, computational, and CD exciton chirality approaches. Trigonoliimine A showed modest anti-HIV-1 activity (EC(50) = 0.95 microg/mL, TI = 7.9).

Anti-Tobacco Mosaic Virus (TMV) Quassinoids from Brucea javanica (L.) Merr.

Two new quassinoids, javanicolide E (1) and javanicolide F (2), along with fifteen known C-20 quassinoids were isolated from the seeds of Brucea javanica (L.) Merr. The antitobacco mosaic virus (TMV) activity of these quassinoids was screened by the conventional half-leaf and leaf-disk method along with Western blot analysis. All of the seventeen quassinoids showed potent anti-TMV activity. Among them, eight compounds, brusatol (3), bruceine B (4), bruceoside B (5), yadanzioside I (6), yadanzioside L (7), bruceine D (8), yadanziolide A (9), and aglycone of yadanziolide D (17), showed strong antiviral activities, with IC(50) values in the range of 3.42-5.66 microM, and were much more effective than the positive control, ningnanmycin (IC(50) = 117.3 microM). The antiviral structure-activity relationships of quassinoids against TMV were also discussed.

Tobacco Mosaic Virus (TMV) Inhibitors from Picrasma quassioides Benn

To investigate natural inhibitors against tobacco mosaic virus (TMV) from plants, 10 known beta-carboline alkaloids and one quassinoid have been isolated from MeOH extract of the wood of Picrasma quassioides Benn. These compounds were screened for their inhibitory activities against tobacco mosaic virus (TMV). The activity of each compound against TMV infection and replication was tested using a half-leaf assay method, a leaf-disk method, and Western blotting analyses. All of the beta-carboline alkaloids showed moderate anti-TMV activities and exhibited synergistic effects when combined with the quassinoid nigakilactone B (11). To our knowledge, this is the first report on anti-TMV activity of beta-carbolines and their synergistic effects against TMV when combined with a quassinoid.

Protein kinase C controls lysosome biogenesis independently of mTORC1

Lysosomes respond to environmental cues by controlling their own biogenesis, but the underlying mechanisms are poorly understood. Here we describe a protein kinase C (PKC)-dependent and mTORC1-independent mechanism for regulating lysosome biogenesis, which provides insights into previously reported effects of PKC on lysosomes. By identifying lysosome-inducing compounds we show that PKC couples activation of the TFEB transcription factor with inactivation of the ZKSCAN3 transcriptional repressor through two parallel signalling cascades. Activated PKC inactivates GSK3β, leading to reduced phosphorylation, nuclear translocation and activation of TFEB, while PKC activates JNK and p38 MAPK, which phosphorylate ZKSCAN3, leading to its inactivation by translocation out of the nucleus. PKC activation may therefore mediate lysosomal adaptation to many extracellular cues. PKC activators facilitate clearance of aggregated proteins and lipid droplets in cell models and ameliorate amyloid β plaque formation in APP/PS1 mouse brains. Thus, PKC activators are viable treatment options for lysosome-related disorders.

Peganumine A, a β-Carboline Dimer with a New Octacyclic Scaffold from Peganum harmala

Peganumine A (1), a new dimeric β-carboline alkaloid characterized by a unique 3,9-diazatetracyclo[6.5.2.0(1,9).0(3,8)]pentadec-2-one scaffold, was isolated from the seeds of Peganum harmala. The structure including the absolute configuration was determined by spectroscopic data, X-ray crystallography, ECD calculation, and CD exciton chirality approaches. Compound 1 showed moderate cytotoxic activity against MCF-7, PC-3, and HepG2 cells and selective effects on HL-60 cells with an IC50 value of 5.8 μM.

Indole alkaloids from Ervatamia chinensis

Four vobasinyl-ibogan type bisindole alkaloids, ervachinines A-D (1-4), along with 12 known terpenoid indole alkaloids, were isolated from the whole plant of Ervatamia chinensis. Their structures were elucidated by analysis of spectroscopic data, including 1D and 2D NMR, and the absolute configurations of 1-4 were determined by CD exciton chirality method. All of the compounds were evaluated for in vitro cytotoxicity against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480. Bisindole alkaloids 1-6 exhibited inhibitory effects, with IC(50) values comparable to those of cisplatin.

Cipadonoid A, a Novel Limonoid with an Unprecedented Skeleton, from Cipadessa cinerasecns

Cipadonoid A ( 1), a novel limonoid with an unprecedented skeleton, was isolated from the leaves of Cipadessa cinerasecns. Its structure and relative configuration were determined by spectroscopic analysis and computer modeling. 1 represents a new type of limonoid, characterized by a rearranged tetrahydropyranyl ring B incorporating usually exocyclic C-30. A possible biosynthetic pathway of 1 was also proposed.

Daphenylline, a New Alkaloid with an Unusual Skeleton, from Daphniphyllum longeracemosum

A new alkaloid, daphenylline (1), with an unprecedented rearranged 22-nor-calyciphylline skeleton, was isolated from the fruits of Daphniphyllum longeracemosum. Its structure and stereochemistry were elucidated on the basis of spectroscopic and computational approaches. A plausible biosynthetic pathway of 1 was also proposed.

Trigonosins A-F, daphnane diterpenoids from Trigonostemon thyrsoideum.

Phytochemical study of the roots of Trigonostemon thyrsoideum led to the isolation of four new oxygenated daphnane-type diterpenoids, trigonosins A-D (1-4), and two new modified daphnanes, trigonosins E and F (5 and 6). The structures and relative configurations were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments. All compounds isolated were evaluated for their cytotoxicity against HL-60, A549, and MCF-7 human cancer cell lines.

Aphanamixoid A, a Potent Defensive Limonoid, with a New Carbon Skeleton from Aphanamixis polystachya

Aphanamixoid A (1), a limonoid with a new carbon skeleton, along with its biogenetically related limonoid aphanamixoid B (2), was isolated from the leaves and twigs of Aphanamixis polystachya . Their structures with the absolute stereochemistry were determined by spectroscopic analysis, X-ray crystallography and computational methods. The significant antifeedant activity of 1 against the generalist plant-feeding insect Helicoverpa armigera (EC50 = 0.015 μmol/cm(2)) suggested it may be a potent defensive component of A. polystachya.