Bioactivity-guided isolation of anti-inflammatory limonins from Chukrasia tabularis.

Chukrasia tabularis is an economically important tree and widely cultured in the southeast of China. Its barks, leaves, and fruits are consumed as a traditional medicine and perceived as a valuable source for bioactive limonin compounds. The extracts from root barks of C. tabularis showed significant anti-inflammatory effect. The aim of this research was to explore the material basis of C. tabularis anti-inflammatory activity, and to purify and identify anti-inflammatory active ingredients. By a bioassay-guided isolation of dichloromethane fraction obtained two novel phragmalin limonins, Chukrasitin D and E (1 and 2), together with 12 known limonins (3-14). The chemical structure of these compounds is determined on the basis of extensive spectral analysis and chemical reactivity. In addition, the activities of these isolated limonins on the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), and nuclear factor kappa B (NF-κB) in RAW264.7 cells induced by lipopolysaccharide (LPS) were evaluated. Limonins 1 and 2 indicated significant anti-inflammatory activity with IC50 values of 6.24 and 6.13 µM. Compound 1 notably inhibited the production of NF-κB, TNF-α and interleukin 6 (IL-6) in macrophages. The present results suggest that the root barks of C. tabularis exhibited anti-inflammatory effect and the limonins may be responsible for this activity.

Three new phomalone derivatives from a deep-sea-derived fungus Alternaria sp. MCCC 3A00467.

Three new phomalone derivatives, phomalichenones E-G (1-3), and seven known analogues (4-10) were isolated from the cultures of a deep-sea-derived fungus Alternaria sp. MCCC 3A00467. Their structures were elucidated by spectroscopic methods, including the 1D and 2D NMR, and ECD spectrum. Among the compounds isolated, phomalichenone F (2) presented cytotoxic activity against human myeloma cancer U266 cells with IC50 value of 24.99 µg/mL. The most active compound, 10, showed cytotoxicity against U266, HepG2 and A549 cells with IC50 values of 13.26, 14.69 and 24.39 µg/mL, respectively.

Solitumergosterol A, a unique 6/6/6/6/5 steroid from the deep-sea-derived Penicillium solitum MCCC 3A00215.

A unique C30 steroid, solitumergosterol A (1), was isolated from the deep-sea-derived fungus Penicillium solitum MCCC 3A00215. The planar structure and relative configuration of 1 were established mainly on the basis of extensive analysis of its 1D and 2D NMR as well as HRESIMS data, while its absolute configuration was clarified by comparison of the experimental and theoretical ECD spectra. Noteworthily, 1 is a Diels-Alder adduct of a heterogeneous steroid bearing a 6/6/6/6/5 pentacyclic carbon skeleton. Solitumergosterol A (1) exhibited weak in vitro anti-tumor activity against MB231 cells by a RXRα-dependent mechanism.

Anti-Food Allergic Compounds from Penicillium griseofulvum MCCC 3A00225, a Deep-Sea-Derived Fungus.

Ten new (1-10) and 26 known (11-36) compounds were isolated from Penicillium griseofulvum MCCC 3A00225, a deep sea-derived fungus. The structures of the new compounds were determined by detailed analysis of the NMR and HRESIMS spectroscopic data. The absolute configurations were established by X-ray crystallography, Marfey's method, and the ICD method. All isolates were tested for in vitro anti-food allergic bioactivities in immunoglobulin (Ig) E-mediated rat basophilic leukemia (RBL)-2H3 cells. Compound 13 significantly decreased the degranulation release with an IC50 value of 60.3 µM, compared to that of 91.6 µM of the positive control, loratadine.

Two new phenylspirodrimanes from the deep-sea derived fungus Stachybotrys sp. MCCC 3A00409.

Two new phenylspirodrimanes, stachybotrin H (1) and stachybotrysin H (9) together with eleven known analogues (2-8, 10-13) were isolated from deep-sea derived Stachybotrys sp. MCCC 3A00409. Their structures were determined by extensive NMR data and mass spectroscopic analysis. Compounds 9-12 showed weak cytotoxicity against three human cancer cell lines K562, Hela and HL60 with IC50 in the range of 18.5-52.8 µM.

Diterpenoids from Wedelia prostrata and Their Derivatives and Cytotoxic Activities.

One new ent-kaurane diterpenoid, 11ß,16α-dihydroxy-ent-kauran-19-oic acid (1), together with eight known analogues 2 - 9 were isolated from the aerial parts of Wedelia prostrata. One of the acidic diterpenoids, kaurenoic acid (3), was converted to seven derivatives, 10 - 16. All compounds were evaluated for their cytotoxic activity in vitro against human leukemia (K562), liver (HepG-2), and stomach (SGC-7901) cancer cell lines. Only four kaurenoic acid derivatives, 13 - 16, with 15-keto and substitutions at C(19) position, exhibited notable cytotoxic activities on these tumor cell lines with IC50 value ranging from 0.05 to 3.71 µm. Compounds 10 - 12, with oxime on C(15) showed moderate inhibitory effects and compounds 1 - 9 showed no cytotoxicities on them. Structure-activity relationships were also discussed based on the experimental data obtained. The known derivative, 15-oxokaurenoic acid 4-piperdin-1-ylbutyl ester (17), induced typical apoptotic cell death in colon SW480 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis.

[The modified restriction of amino acids of HVR1, HVR2, HVR5, HVR7 in human adenovirus serotype 3 hexon].

The limitation of traditional Ad vectors result in wide application of capsid-incorporation of antigens into adenovirus capsid proteins, but usually it can't rescue virus successfully when we engineered the hypervariable regions (HVRs) of hexon in adenovirus serotype 3(Ad3) vector. So we deleted or retained some amino acids in HVR1, HVR2, HVR5, HVR7 predicted by bioinformatics, constructed recombinant Ad3 vector pBRAddeltaE3GFP-mHexon, and transfected it into AD293 cell to confirm the influence on the virus rescue. These data of amino acids that can be deleted or retained in the HVRs of Ad3 vector should provide operating foundation for antigen capsid-incorporation strategy in human adenovirus serotype 3, and also lay the groundwork for application of expressing foreign antigens in the hexon of human adenovirus serotype 3 as a platform of multivalent vaccine vectors.