Biomimetic Total Synthesis of Bimagnolignan: A Natural Anti-Breast Cancer Agent.

A short scalable biomimetic route to bioactive natural product bimagnolignan (1) was accomplished. Compound 1 was successfully prepared through a three-step metal-free synthesis from honokiol (2). Alternatively, 1 was also synthesized by biomimetic transformations that mimic tyrosinase in four steps. The key reactions feature a regioselective acetylation, a highly efficient C(sp2)-H oxidation, a cascade aerobic oxidative cyclization/coupling, and a Cu-catalyzed direct oxidative coupling. In addition, cell-based assays validate that 1 is a promising natural lead for HER2-positive breast cancer treatment.

Anti-inflammatory and analgesic effects of Streblus indicus.

The bark of Streblus indicus, a Dai medicine in China, has been listed in the Chinese Materia Medica as possessing hemostatic and analgesic properties. Ethnic medicine books record that its bark or leaves for the treatment of mumps and lymphoma. However, according to the literature survey, anti-inflammatory and analgesic studies available for leaves and branches of S. indicus have been seldom reported so far. The current study focuses on the metabolites of S. indicus bark and leaves responsible for anti-inflammatory and analgesic effects on the basis of bioactive-included acetic acid writhing, hot-plate, and xylene-induced ear swelling. The secretion of inflammatory mediators, TNF-α, IL-6, IL-1ß, IL-4, and IL-10, were evaluated for their anti-inflammatory by xylene-induced in mouse ear cells. Histological examination was used to assess the anti-inflammatory and analgesic effects of the branches and leaves of S. indicus, and Western blot analysis determined the mechanism of the methanolic extract of branches and leaves. Different metabolites of S. indicus significantly alleviated analgesic and anti-inflammatory effects, with no discernable differences among them. All metabolites decreased the levels of TNF-α, IL-1ß, and IL-6 and increased the levels of IL-4 and IL-10. The analgesic and anti-inflammatory mechanism of the methanolic extract was related to the NF-kB signaling pathway. These results not only would account for scientific knowledge for the traditional application of S. indicus, but also provide a credible theoretical foundation for the further development of anti-inflammatory and analgesic agents.

(±)-Gentiovarisin A and gentiovarisin B, unusual secoiridoid dimer skeletons from gentiopicroside.

Gentiana scabra, a famous traditional Chinese medicine (TCM), has been documented in Chinese Pharmacopoeia for the treatment of hepatitis. Its index component gentiopicroside could not be detected in the decoction, which suggested that the quality control of the TCM with this ingredient needs attention. The transformed products were obtained from gentiopicroside, mimicking the traditional process of G. scabra. Further investigation of the heat-transformed products yielded two secoiridoid dimers, gentiovarisin A (1) and B (2), with an unprecedented 6/6/6/6/6-fused pentacyclic skeletons. Their structures were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction analysis, and the absolute configurations of 1 were confirmed as (+)-1 and (-)-1 by ECD method. Plausible transformation pathways of the isolates were also proposed. Compounds 1 and 2 exhibited in vitro hepatoprotective activity similar to gentiopicroside, while (+)-1 displayed a more potent hepatoprotective activity than N-Acetyl-L-cysteine.

Involucrasin C, Anti-Inflammatory 2,3-Dihydro-1H-Indene Derivative from Chinese Dai Ethnic Medicine Shuteria involucrata.

(±)-Involucrasin C (1), a pair of new 2,3-dihydro-1H-indene enantiomers, along with an enantiomeric analog (2), were isolated from Shuteria involucrata. Their structures were established by the basis of comprehensive spectroscopic data analysis and X-ray crystallographic diffraction. Both 1 and 2 significantly inhibited the secretion of pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß, suggesting that these two natural 2,3-dihydro-1H-indene derivatives may be active components of S. involucrata and may block inflammation in the initial stage.

(±)-Involucrasins A and B, two pairs of flavanone enantiomers from Shuteria involucrata and their inhibitory effects on the proliferation of various cancer cell lines.

(±)-Involucrasins A (1) and B (2), two pairs of flavanone enantiomers were isolated from Shuteria involucrata. Structurally, both 1 and 2 are rare representatives of 5-dehydroxy/5-demethoxy 2',3',4'-trisubstituted flavanones. Their structures were elucidated on the basis of comprehensive spectroscopic data analysis and comparison with the literature data. Involucrasin B (2) exhibited moderate anti-proliferative activity against Caco-2, MCF-7, MDA-MB-468, and HCT116 cell lines with IC50 values ranging from 7.9-22.7 µM. Involucrasin A (1) exhibited weak inhibitory activity against Caco-2 and MCF-7 cell lines with IC50 values of 25.8 and 26.5 µM, respectively.

Sweritranslactone D, a hepatoprotective novel secoiridoid dimer with tetracyclic lactone skeleton from heat-transformed swertiamarin.

Swertia mileensis, known as Qing-Ye-Dan (QYD), has been documented in Chinese Pharmacopoeia to cure hepatitis. Interestingly, its announced main active component, swertiamarin, could not be detected in the decoction, which indicated that the efficacy of QYD might be attributed to heat-transformed products of swertiamarin (HTPS). Further investigation on HTPS led to the isolation of sweritranslactone D (1), a novel secoiridoid dimer possessing a tetracyclic lactone skeleton, with better hepatoprotective activity than N-acetyl-L-cysteine in vitro.