Qin-Shi Zhao

The functional roles of lipid rafts in T cell activation, immune diseases and HIV infection and prevention.

The first appearance of lipid rafts, or lipid rafts-like structure, was occasionally observed by cryo-electronic microscopy in 1980s as cavity, such as caveolae. However, the fully understanding of lipid raft was attributed by the studies of T cell activation, virus entry/budding, and other membrane events. During the interaction of T cell and antigen presenting cell, a highly organized structure is formed at the interface of the two cells, where cholesterol and sphingolipids are enriched, and form a liquid ordered phase that facilitates the signaling proteins on and off. Lipid rafts are also involved in virus entry and assembly. In this review, we will discuss cholesterol-sphingolipid floating microdomain, the lipid raft as a unique compartment of the plasma membrane, with biological functions that ensure correct intracellular traffic of proteins and lipids, such as protein-protein interactions by concentrating certain proteins in these microdomains, while excluding others. We also discuss the disruption of lipid rafts is related to different diseases and aging, and we especially exploit the lipid rafts as pharmaceutical targets for anti-virus and anti-inflammation, particularly a new approach to control HIV infection for AIDS prevention and protection by inhibition or disruption of lipid rafts.

Qualitative and quantitative analysis of diterpenoids in Salvia species by liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

An on-line ultra-high-performance liquid chromatography (UHPLC) coupled with photodiode-array detection and quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) method has been optimized and established for the qualitative and quantitative analysis of the important diterpenoids in the methanol extracts of 12 Salvia species. Specific marker components were identified for the classification of the Salvia samples by principal component analysis. The accurate mass measurement within 3 ppm error for all the protonated molecules and subsequent fragment ions offers higher quality structural information for interpretation of fragmentation pathways of various groups of diterpenoids. Thus, a total of 21 diterpenoids from different Salvia species were separated within 10 min, and were unequivocally or tentatively identified via comparisons with authentic standards and literature. This UHPLC-QTOF-MS/MS method was validated to be sensitive, precise and accurate with the limit of detections at 3.0-16 ng/ml, and the overall intra-day and the inter-day variations less than 3%. The recovery of the method was in the range of 96.2-101.8%, with relative standard deviation (RSD) less than 3.0%. The results demonstrated that the qualitative and quantitative differences in diterpenoids were not only useful for chemotaxonomy in some Salvia species but also for the standardization and differentiation of large numbers of similar samples.

Lycojapodine A, a Novel Alkaloid from Lycopodium japonicum

Lycojapodine A, a novel C(16)N-type Lycopodium alkaloid with an unprecedented 6/6/6/7 tetracyclic ring system, was isolated from the club moss Lycopodium japonicum. The structure and relative stereochemistry were elucidated on the basis of spectroscopic data and were further confirmed by X-ray analysis. A possible biosynthetic pathway for 1 was proposed. Its inhibitory activity on acetylcholinestrease and anti-HIV-1 activity were also evaluated.

Lancifodilactone A, a novel bisnortriterpenoid from Schisandra lancifolia

A novel bisnortriterpenoid, lancifodilactone A, has been isolated from the leaves and stems of Schisandra lancifolia. Its structure and stereochemistry were determined primarily from ID and 2D NMR spectroscopic data, and were confirmed by a single crystal X-ray analysis

Bioassay and Ultraperformance Liquid Chromatography/Mass Spectrometry Guided Isolation of Apoptosis-Inducing Benzophenones and Xanthone from the Pericarp of Garcinia yunnanensis Hu

Bioassay and ultraperformance liquid chromatography/photodiode array/mass spectrometry (UPLC/PDA/MS) guided isolation of the apoptosis-inducing active metabolites on HeLa-C3 cells from the pericarp of Garcinia yunnanensis (Guttiferae) yielded five active compounds, including the new garciyunnanins A (1) and B (2). The structures of the compounds were elucidated by comprehensive nuclear magnetic resonance and mass spectrometry analysis. Garciyunnanin B (2), featured with a natural tetracyclic xanthone skeleton derived from a polyisoprenylated benzophenone, is structurally interesting since it can be seen as an evidence of the previously described cyclization of garcinol by 2,2-diphenyl-1-picrylhydrazyl (DPPH). Garciyunnanin A (1) contains a 3-monohydroxy benzophenone skeleton, which is rarely found in Garcinia species. Both new compounds induce HeLa-C3 cells into apoptosis after 72 h of incubation at 15 microM. It is noteworthy that oblongifolin C (4), the major constituent of this plant, has proved to be the most active one among the isolates for inducing apoptotic cell death in cervical cancer derived HeLa-C3 sensor cells.

Hypercohin A, a new polycyclic polyprenylated acylphloroglucinol possessing an unusual bicyclo[5.3.1]hendecane core from Hypericum cohaerens

Hypercohin A (1), an unprecedented polycyclic polyprenylated acylphloroglucinol featuring with an unusual bicyclo[5.3.1]hendecane core, was isolated from Hypericum cohaerens. Its structure and absolute configurations were elucidated by extensive NMR methods and crystal X-ray diffractions of its p-bromobenzoate ester (2).

Macrophyllionium and Macrophyllines A and B, Oxindole Alkaloids from Uncaria macrophylla

An unusual oxindole alkaloid inner salt, macrophyllionium (1), and a pair of new tetracyclic oxindole alkaloids, macrophyllines A (2) and B (3), together with six known alkaloids, were isolated from the aerial parts of Uncaria macrophylla. Corynantheidine (8) exhibited moderate cytotoxicity against HL-60 and SW480 cells with IC(50) values of 13.96 and 23.28 μM, respectively. Dihydrocorynantheine (9) exhibited significant vasodilating activity against phenylephrine-induced contraction in rat thoracic aorta rings (IC(50) = 6.73 μg/mL). In addition, compounds 2, 6, and 9 showed weak inhibitory action on KCl-induced contraction.

Lycopalhine A, a novel sterically congested Lycopodium alkaloid with an unprecedented skeleton from Palhinhaea cernua

A novel sterically congested Lycopodium alkaloid named lycopalhine A (1) that possesses a fused hexacyclic (5/5/5/6/6/6) ring system comprising a 5,9-diaza-tricyclo[6.2.1.0(4,9)]undecane moiety and a tricyclo[5.2.1.0(4,8)]decane moiety was isolated from Palhinhaea cernua L. The structure and absolute configuration were determined by spectroscopic and computational methods.

Construction of Tetracyclic 3-Spirooxindole through Cross-Dehydrogenation of Pyridinium: Applications in Facile Synthesis of (±)-Corynoxine and (±)-Corynoxine B

A facile and straightforward method was developed to construct the fused tetracyclic 3-spirooxindole skeleton, which exists widely in natural products. The formation of the tetracyclic 3-spirooxindole structure was achieved through a transition-metal-free intramolecular cross-dehydrogenative coupling of pyridinium, which were formed in situ by the condensation of 3-(2-bromoethyl)indolin-2-one derivatives with 3-substituted pyridines. As examples of the application of this new methodology, two potentially medicinal natural products, (±)-corynoxine and (±)-corynoxine B, were efficiently synthesized in five scalable steps.

Terpenoids and Norlignans from Metasequoia glyptostroboides

Four new terpenoids, metaseglyptorin A (1), metasequoic acid C (2), 12α-hydroxy-8,15-isopimaradien-18-oic acid (3), and (-)-acora-2,4(14),8-trien-15-oic acid (4), and three new norlignans, metasequirins D-F (5-7), were isolated from Metasequoia glyptostroboides, together with 15 known compounds. Structures of the new compounds were determined by analysis of their spectroscopic data, and the absolute configuration of 7 was established by the modified Mosher method. All of the compounds were evaluated for cytotoxicity against five human tumor cell lines.