Short Total Synthesis of (±)-Gelliusine E and 2,3'-Bis(indolyl)ethylamines via PTSA-Catalyzed Transindolylation.

A first and short total synthesis of the marine sponge 2,3'-bis(indolyl)ethylamine (2,3'-BIEA) alkaloid (±)-gelliusine E was performed in both a three-step divergent approach and a one-pot three-component approach with an overall yield of up to 58%. A key feature of the novel strategy is PTSA-catalyzed transindolylation of the readily synthesized 3,3'-BIEAs with tryptamine derivatives. The structure of the isolated natural product is revised as protonated (±)-gelliusine E (4'). By design, this modular route allows the rapid synthesis of other members of the 2,3'-BIEA family, for example, (±)-6,6'-bis-(debromo)-gelliusine F and analogues with step economy, operational simplicity, and reduced waste. Furthermore, their cytotoxicity in breast cancer cells was investigated.

Unified synthesis and cytotoxic activity of 8-O-methylfusarubin and its analogues.

A simple and unified synthesis of four related pyranonaphthoquinone natural products, e.g. 8-O-methylfusarubin, 8-O-methylanhydrofusarubin, fusarubin and anhydrofusarubin, is reported. The key synthetic features include the precedented Diels-Alder cycloaddition to assemble the naphthalene skeleton, selective formylation and acetonylation and intramolecular acetalization to construct the pyran ring. Manipulation of the oxidation state of the naphthoquinone core was performed to construct the two analogues, fusarubin and anhydrofusarubin. This work also highlights an unprecedented directing effect of the hydroxymethylene group in the selective hypervalent iodine-mediated quinone oxidation. The four synthetic compounds were evaluated for their in vitro cytotoxic activities against six human cancer cells. 8-O-Methylfusarubin was the most potent analogue and displayed excellent cytotoxic activity against MCF-7 breast cancer cells with an IC50 value of 1.01 µM with no cytotoxic effect on noncancerous Vero cells, which could potentially be a promising lead compound for anti-breast cancer drug discovery.

Synthesis and characterization of new hydrolytic-resistant dental resin adhesive monomer HMTAF.

Hydrolytic and enzymatic degradation of resin adhesives over time has been mainly attributed to secondary caries formation of methacrylate-based tooth-colored resin-based composite restorations. Ability of resin adhesive monomers to infiltrate into demineralized dentin forming stiff polymer matrix and potentially bonding to tooth structure is also a crucial property. The only commercially available antibacterial monomer, 12-methacryloyloxydodecyl pyridinium bromide (MDPB), is a quaternary ammonium methacrylate. This methacrylate monomer undergoes hydrolytic degradation, and could not bond to tooth structure. In this study, a new hydrolytic resistant monomer HMTAF was synthesized. It is methacrylamide-based monomer that, unlike methacrylate, is highly resistant to hydrolysis. Its molecular structure has particular functional groups; quaternary ammonium fluoride salt with potential antibacterial fluoride-releasing activity, hydroxyl and amide group with hydrogen bonding potential to dentin collagen. Hydroxyl group also increases monomer hydrophilicity for better penetration into water-saturated dentin and sufficient resin-dentin bond. The synthesized HMTAF and its polymer showed no hydrolytic degradation in acidic environment, while MDPB and its polymer were partially decomposed under this challenge. The conversion of monomer HMTAF to polymer was illustrated by FT-IR. The results indicated that HMTAF is highly resistant to hydrolysis, polymerizable and non-cytotoxic to Vero cell lines. It is a potential monomer to be incorporated into resin adhesives for improving hydrolytic and enzymatic resistance.

4-methoxycinnamyl p-coumarate isolated from Etlingera pavieana rhizomes inhibits inflammatory response via suppression of NF-κB, Akt and AP-1 signaling in LPS-stimulated RAW 264.7 macrophages.

BACKGROUND: 4-methoxycinnamyl p-coumarate (MCC) was isolated from rhizomes of Etlingera pavieana by bioactivity-guided isolation, however, the molecular mechanism underlying its anti-inflammatory activity remains inadequately understood. PURPOSE: In this study, we elucidated the suppressive effect of MCC on LPS-induced expression of inflammatory mediators and the molecular mechanisms responsible for anti-inflammatory activities in RAW 264.7 macrophages. METHODS: Cell viability of MCC-treated RAW 264.7 macrophage was measured by MTT assay. Anti-inflammatory activity was evaluated by measurement of NO, PGE2, and cytokine production in LPS-stimulated cells. qRT-PCR and Western blotting analysis were used to investigate mRNA and protein levels of inflammatory responsive genes. NF-κB activation and transactivation activity were determined by immunofluorescence and reporter gene assay, respectively. RESULTS: MCC considerably suppressed both the production of NO, PGE2, IL-1ß as well as TNF-α and their expression. MCC inactivated NF-κB by reducing phosphorylation of IκBα and inhibiting NF-κB p65 nuclear translocation. Also, MCC significantly inhibited NF-κB transactivation activity. However, the inhibitory effect of MCC was independent of the MAPK signaling pathway. Furthermore, MCC significantly decreased phosphorylation of Akt and c-Jun, a main component of AP-1. CONCLUSION: These findings suggest that the anti-inflammatory effect of MCC could be mediated by the inhibition of LPS-induced expression of inflammatory mediators by down-regulation of the NF-κB, Akt and AP-1 signaling pathways in murine macrophages.