5-Deoxyflavones with Cytotoxic Activity from <i>Mimosa diplotricha</i>

Bioassay-guided isolation of Mimosa diplotricha led to the isolation of four new 5-deoxyflavones, diplotrins A–C (1–3) and diplotasin (4), together with 12 known flavonoids, flavonolignans, and triterpenoids. On the basis of spectroscopic evidence, compounds 1–4 were characterized as 2′,5′-dihydroxy-3,7,8,4′-tetramethoxyflavone (1), 3′-hydroxy-3,7,8,4′-tetramethoxyflavone (2), 2′-hydroxy-7,4′,5′-trimethoxyflavone (3), and 4-hydroxy-3,10,11-trimethoxyisochromeno-[4,3-b]-chromen-7(5H)-one (4). The cytotoxic effects of these isolated compounds were evaluated against the A549, AGS, HT-29, and PC3 human cancer cell lines. Compounds 2 and 5″-methoxyhydnocarpin-D (5) showed the most potent antiproliferative activity

Meroterpenoids and Chalcone-Lignoids from the Roots of <i>Mimosa diplotricha</i>

Six new meroterpenoids, diplomeroterpenoids A–F (<b>1</b>–<b>6</b>), two new chalcone-lignoids, diplochalcolins A and B (<b>7</b>, <b>8</b>), and 13 known compounds were isolated from the root extract of <i>Mimosa diplotricha</i>. Diplomeroterpenoids A–F consist of a 4<i>H</i>-chromen-4-one and a diterpenoid unit, and their absolute configurations were determined by X-ray crystallographic analysis. Compounds <b>1</b>–<b>3</b> and <b>5</b> showed potent inhibitory activity on protein farnesyl transferase, with IC₅₀ values from 5.0 to 8.5 μM. Compound <b>1</b> showed antiproliferative activity against human hepatoblastoma HepG2 cells with a GI₅₀ value of approximately 8.6 μM

Palladium-Catalyzed Cascade <i>Endo</i>-<i>dig</i> Cycloisomerization and Olefination with Alkenes to Access Fused Oxatricyclic Compounds

A novel cascade Pd(II)-catalyzed endo-dig cycloisomerization and olefination reaction of 2-benzyl-3-alkynyl chromones with activated/unactivated alkenes has been developed for the synthesis of fused oxatricyclic compounds. This concise one-pot synthetic approach was applied to the difunctionalization of unbiased alkynes based on 2-benzyl-3-(alkynyl)-4H-chromen-4-one via O-attack endo-dig cycloisomerization, followed by olefination with both activated and unactivated alkenes

Cytotoxic Hexacyclic Triterpene Acids from <i>Euscaphis japonica</i>

Six hexacyclic triterpene acids (1−6), named euscaphic acids A−F, and eight known triterpene acid compounds (7−14) were isolated from an ethanolic extract of twigs of Euscaphis japonica. Compounds 8 and 10 were isolated for the first time from a natural source. Triterpenes 1−6 possess hexacyclic skeletons with a 13α,27-cyclopropane ring. Structural elucidation of compounds 1−6 was established by spectroscopic methods, especially 2D NMR techniques (1H−1H COSY, HMQC, HMBC, and NOESY). Compounds 3, 4, and 14 showed significant cytotoxicity against different cancer cell lines [IC50 = 2.54 (NCI-H460), 3.61 (MCF-7), and 3.27 μM (CEM) for 3, 4, and 14, respectively]

Cytotoxic Polyisoprenyl Benzophenonoids from <i>Garcinia subelliptica</i>

Six new polyisoprenyl benzophenonoids, (±)-garcinialiptone A (1, 2), garcinialiptone B (3), (−)-cycloxanthochymol (4), garcinialiptone C (5), and garcinialiptone D (6), along with three known compounds, xanthochymol (7), isoxanthochymol (8), and cycloxanthochymol (9), were isolated from the fruits of Garcinia subelliptica. The structures of 1−6 were elucidated by spectroscopic analysis. Biological evaluation showed that all compounds 1−9 exhibited cytotoxic activity against a small panel of human tumor cell lines (A549, DU145, KB, vincristine-resistant KB)

Structure-Based Discovery of Triphenylmethane Derivatives as Inhibitors of Hepatitis C Virus Helicase

Hepatitis C virus nonstructural protein 3 (HCV NS3) helicase is believed to be essential for viral replication and has become an attractive target for the development of antiviral drugs. A fluorescence resonant energy transfer helicase assay was established for fast screening of putative inhibitors selected from virtual screening using the program DOCK. Soluble blue HT (1) was first identified as a novel HCV helicase inhibitor. Crystal structure of the NS3 helicase in complex with soluble blue HT shows that the inhibitor bears a significantly higher binding affinity mainly through a 4-sulfonatophenylaminophenyl group, and this is consistent with the activity assay. Subsequently, fragment-based searches were utilized to identify triphenylmethane derivatives for more potent inhibitors. Lead optimization resulted in a 3-bromo-4-hydroxyl substituted derivative 12 with an EC50 value of 2.72 μM to Ava.5/Huh-7 cells and a lower cytotoxicity to parental Huh-7 cells (CC50 = 10.5 μM), and it indeed suppressed HCV replication in the HCV replicon cells. Therefore, these inhibitors with structural novelty may serve as a useful scaffold for the discovery of new HCV NS3 helicase inhibitors