ABSTRACT
A chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes (1 and 2) together with 14 known compounds (3-16) by using multiple chromatographic techniques. New compounds (1 and 2) were obtained and identified by spectroscopic methods (HR-ESI-MS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF-α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)-α production with IC50 value of 6.16±0.14â µM. Whereas, compounds (1, 3, and 6) showed the significant inhibition (IC50 values ranging from 9.41 to 14.54â µM), and compounds (2, 4, 9, 10, 13, 15, and 16) exhibited moderate inhibition (IC50 values ranging from 19.27 to 40.64â µM) toward TNF-α production, respectively.
Subject(s)
Kadsura , Lignans , Kadsura/chemistry , Tumor Necrosis Factor-alpha , Lignans/pharmacology , Lignans/chemistry , Anti-Inflammatory Agents/pharmacology , Phenols , Molecular StructureABSTRACT
Sixteen sesquiterpenoids (1 - 16), including two new compounds namely saussucostusosides A and B (1 and 2), were isolated from the roots of Saussurea costus by various chromatographic separations. Their structures were elucidated by 1 D and 2 D NMR and HR-QTOF-MS experiments. Among isolated compounds, costunlide (6), 3ß-[4-hydroxymethacryloyloxy]-8α-hydroxycostunolide (10) and 11ß,13-dihydrozaluzanin C (16) exhibited potent inhibitory effects on LPS-induced NO production in RAW264.7 cells with IC50 values of 7.08 ± 0.34, 2.40 ± 0.06 and 5.55 ± 0.24 µM, respectively.
Subject(s)
Saussurea/chemistry , Sesquiterpenes/isolation & purification , Animals , Carbon-13 Magnetic Resonance Spectroscopy , Inhibitory Concentration 50 , Lipopolysaccharides/pharmacology , Mice , Nitric Oxide/biosynthesis , Plant Extracts/chemistry , Plant Roots/chemistry , Proton Magnetic Resonance Spectroscopy , RAW 264.7 Cells , Sesquiterpenes/chemistryABSTRACT
Chemical investigation of the aerial parts of Andrographis paniculata resulted in isolation of nine compounds, including a new ent-labdane diterpenoid, andrographic acid methyl ester (1), a new chalcone glucoside, pashanone glucoside (5), and seven known metabolites, andrograpanin (2), andrographolide (3), andropanolide (4), andrographidine A (6), andrographidine F (7), 6-epi-8-O-acetyl-harpagide (8), and curvifloruside F (9). Their chemical structures were elucidated based on comprehensive analyses of the spectroscopic data, including NMR and MS. Among the isolated compounds, andropanolide exerted cytotoxicity toward LNCaP, HepG2, KB, MCF7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 31.8 to 45.9 µM. In addition, andropanolide significantly inhibited the overproduction of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with an IC50 value of 13.4 µM.
Subject(s)
Andrographis/chemistry , Diterpenes/chemistry , Flavonoids/chemistry , Andrographis/metabolism , Animals , Cell Line, Tumor , Cell Survival/drug effects , Diterpenes/isolation & purification , Diterpenes/pharmacology , Flavonoids/isolation & purification , Flavonoids/pharmacology , Humans , Lipopolysaccharides/toxicity , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Magnetic Resonance Spectroscopy , Mice , Molecular Conformation , Nitric Oxide/metabolism , Plant Components, Aerial/chemistry , Plant Components, Aerial/metabolism , RAW 264.7 CellsABSTRACT
A series of novel hydroxamic acids bearing artemisinin skeleton was designed and synthesized. Some compounds in this series exhibited moderate inhibition against the whole cell HDAC enzymes. Especially, compound 6g displayed potent cytotoxicity against three human cancer cell lines, including HepG2 (liver cancer), MCF-7 (breast cancer) and HL-60 (leukemia cancer), with IC50 values of 2.50, 2.62 and 1.28µg/mL, respectively. Docking studies performed with two potent compounds 6a and 6g using Autodock Vina showed that both compounds bound to HDAC2 with relatively high binding affinities from -7.1 to 7.0kcal/mol compared to SAHA (-7.4kcal/mol). It was found in this research that most of the target compounds seemed to be more cytotoxic toward blood cancer cells (HL-60) than liver (HepG2), and breast (MCF-7) cancer cells.
