Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on the ability of bile acids for vectorializing the cytostatic activity of other agents, we have designed and synthesized a new bile acid cholylglycinato Au(III) complex, named Bamet-A1. It has been characterized by means of EA (elemental analysis), FT-IR, NMR, FAB-MS (fast atom bombardment-mass spectrometry) and Vis-UV techniques. This characterization allowed us to propose a structure of the type [Au CG(O) CG(N,O) Cl] for the neutral complex, which has the composition C522H84N2O12AuCl and is very soluble in water, methanol, ethanol and DMSO (dimethylsulfoxide). The study in aqueous solution suggested a redox process for its transformation, which is accompanied by the appearance of colloidal gold phase. The behavior in 4 mM NaCl water (in order to mimic the cytoplasmatic fluid) was similar to that observed in water, while in a 150 mM NaCl (similar to extracellular fluid and serum), the apparition of a dark blue precipitate was observed. This complex displays fluorescence, which does not change when incubated with DNA obtained from E. coli. Bamet-A1 was found to inhibit the growth of a variety of cell lines. The cytostatic effect was mild against human hepatoma HepG2, mouse hepatoma Hepa 1-6, rat hepatoma McA RH-7777 and human colon adenocarcinoma LS-174T, and stronger against mouse sarcoma S180-II and mouse leukemia L-1210 cells. The appearance of colloidal Au during the process of hydrolysis under physiological conditions may explains the low cytostatic activity.
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PMID:Structural characterization and cytostatic activity of chlorobischolylglycinatogold(III). 1137 92

A new guaipyridine sesquiterpene alkaloid, cananodine (1), and two new eudesmane sesquiterpenes, cryptomeridiol 11-alpha-L-rhamnoside (2) and gamma-eudesmol 11-alpha-L-rhamnoside (3), along with gamma-eudesmol (4), were isolated from the fruits of Cananga odorata. The structures of compounds 1-3 were established on the basis of NMR and MS methods. In addition, compounds 1-4 and four previously reported alkaloids, cleistopholine (5), N-trans-feruloyltyramine (6), (+)-ushinsunine-beta-N-oxide (7), and lyscamine (8), were evaluated for cytotoxicity against two human hepatocarcinoma cell lines.
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PMID:Cytotoxic constituents of the fruits of Cananga odorata. 1137 55

Three new 11(15-->1)-abeo-taxanes, taxumairols U-W (1-3), have been isolated from extracts of the stem bark of Formosan Taxus mairei. The structures of 1-3 were identified as 5alpha,7beta,9alpha,13alpha,20-pentaacetoxy-2alpha,10beta,15-trihydroxy-11(15-->1)-abeo-taxene, 5alpha,7beta,9alpha,20-tetraacetoxy-2alpha,10beta,13alpha,15-tetrahydroxy-11(15-->1)-abeo-taxene, and 2alpha,4alpha,7beta,10beta-tetraacetoxy-5beta,20-epoxy-9alpha,13alpha,15-trihydroxy-11(15-->1)-abeo-taxene, respectively, on the basis of 2D NMR techniques including COSY, HSQC, HMBC, and NOESY experiments as well as chemical reactions of compounds 1-3 to give 4 (5alpha,7beta,9alpha,10beta,13alpha,20-hexaacetoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene) and 5 (4alpha,7beta,10beta-triacetoxy-9alpha,13alpha-dibenzoxy-5beta,20-epoxy-2alpha,15-dihydroxy-11(15-->1)-abeo-taxene), which are also novel taxane derivatives. Taxumairols U (1) and V (2) exhibited significant cytotoxicities against human hepatoma tumor cells, while taxumairol W (3) was inactive.
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PMID:Taxane diterpenoids from the stem bark of Taxus mairei. 1147 32

A novel type of alpha,beta-butenolide alkaloid, uncinine (1), two novel oxoaporphines, artabonatine C (2) and artabonatine D (3), a new oxazoloaporphine, artabonatine E (4), and a new 7,7'-bisdehydroaporphine, artabonatine F (5), along with 25 known alkaloids, were isolated from Artabotrys uncinatus. The structures of 1-5 were determined using NMR and mass spectral data. Atherospermidine and squamolone exhibited cytotoxicity against hepatocarcinoma cancer cell lines (Hep G(2) and 2,2,15), and the activity of some of the alkaloids in an antithrombin assay is also discussed.
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PMID:The alkaloids of Artabotrys uncinatus. 1157 48

Troglitazone, an oral antidiabetic drug, was reported to cause adverse hepatic effects in certain individuals, leading to its withdrawal from the market. After incubation of troglitazone (100 microM) with the human hepatoma cell line, HepG2 cells, and human primary hepatocytes for 48 to 72 h, an unknown peak was detected in the cell culture. The formation of this peak from troglitazone (100 microM) was also catalyzed by expressed CYP3A4, and further HPLC analysis revealed that there were three metabolites (metabolite A, B, and C) in the peak. The major metabolite, metabolite C (M-C) was identified as an epoxide of a quinone metabolite of troglitazone by comparison with a synthetic authentic standard using tandem mass spectrometry, (1)H NMR, and (13)C NMR analyses. The other two metabolites (M-A and M-B) were stereoisomers with the same molecular weight as M-C, probably produced from M-C by intramolecular rearrangement at the epoxide moiety. M-C showed a weak cytotoxicity in HepG2 cells at low concentrations, as assessed by the crystal violet-staining assay. Since epoxides are generally regarded as the chemically reactive species, M-C may play a role in idiosyncrasy of troglitazone hepatotoxicity via individual differences either in the formation or degradation of this metabolite.
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PMID:Formation of a novel quinone epoxide metabolite of troglitazone with cytotoxicity to HepG2 cells. 1179 84

Two new sesquiterpene lactone glycosides and two new eudesmanolides, along with twelve known compounds were isolated from seeds of Carpesium macrocephalum. The structures of these new compounds were elucidated as 2alpha- O-beta- D-glucopyranosyl-5alpha, 11alpha H-eudesma-4(15)-en-12,8beta-olide ( 1), 2alpha- O-beta- D-glucopyranosyl-5alpha H-eudesma-4(15),11(13)-dien-12,8beta-olide ( 2), 2alpha-acetoxy-5alpha-hydroxy-11alpha H-eudesma-4(15)-en-12,8beta-olide ( 3) and 2alpha,5alpha-dihydroxy-11alphaH-eudesma-4(15)-en-12,8beta-olide ( 4) by spectroscopic methods including 2D NMR techniques ( (1)H- (1)H COSY, (1)H- (1)H NOESY, HMQC, HMBC) and chemical transformations. Compounds 1, 6, 8, 9 and 10 exhibited moderate antibacterial activity, while compound 4 showed appreciable cytotoxic activity against cultured SMMC-7721 (human hepatoma cell).
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PMID:Sesquiterpene lactone glycosides, eudesmanolides, and other constituents from Carpesium macrocephalum. 1214 97

Two new compounds, an ent-isopimarane-type diterpene, 3alpha,12alpha-dihydroxy-ent-8(14),15-isopimaradien-18-al (1), and a dihydrobenzo[b]furan neolignan, (-)-trans-9-acetyl-4,9'-di-O-methyl-3'-de-O-methyldehydrodiconiferyl alcohol (2), along with five known compounds, 7,7'-dihydroxy-6,8'-bicoumarin (bicoumol) (3), 3,4-dimethoxycinnamaldehyde (4), 6-hydroxy-7-methoxycoumarin (isoscopoletin), N-butylaniline, and vanillin, have been isolated from an ethyl acetate-soluble extract of the stem wood of Euphorbiaquinquecostata. The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic data interpretation, and single-crystal X-ray diffraction analysis was used to confirm the structure and relative stereochemistry of 1. The absolute configuration of 1 was established by a convenient Mosher ester procedure in which the sample was treated with MTPA chlorides in deuterated pyridine directly in NMR tubes. All isolates were evaluated for the induction of quinone reductase in Hepa1c1c7 hepatoma cells and for the inhibition of the transformation of murine epidermal JB6 cells.
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PMID:New chemical constituents of Euphorbia quinquecostata and absolute configuration assignment by a convenient Mosher ester procedure carried out in NMR tubes. 1235 Jan 47

A new bicyclic diarylheptanoid, rel-(3S,4aR,10bR)-8-hydroxy-3-(4-hydroxyphenyl)-9-methoxy-4a,5,6,10b-tetrahydro-3H-naphtho[2,1-b]pyran (1), as well as four known compounds, 1,2-dihydro-1,2,3-trihydroxy-9-(4-methoxyphenyl)phenalene (2), hydroxyanigorufone (3), 2-(4-hydroxyphenyl)naphthalic anhydride (4), and 1,7-bis(4-hydroxyphenyl)hepta-4(E),6(E)-dien-3-one (5), were isolated from an ethyl acetate-soluble fraction of the methanol extract of the fruits of Musa x paradisiaca cultivar, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structure and relative stereochemistry of compound 1 were elucidated unambiguously by one- and two-dimensional NMR experiments ((1)H NMR, (13)C NMR, DEPT, COSY, HMQC, HMBC, and NOESY) and single-crystal X-ray diffraction analysis. Isolates 1-5 were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction and a mouse mammary organ culture assay.
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PMID:Constituents of Musa x paradisiaca cultivar with the potential to induce the phase II enzyme, quinone reductase. 1238 Nov 12

A new cyclic heptapeptide phakellistatin 13 (1) had been isolated from the sponge Phakellia fusca Thiele, collected at Yongxing Island of China. Its structure was elucidated as cyclo-(Pro1-Trp-Leu-Thr-Pro2-Gly-Phe) on the basis of MS, UV, IR, and high-field NMR (600 MHz) analysis. The compound was significantly cytotoxic against the human hepatoma BEL-7404 cell line with an ED(50) < 10(-2) microg/mL.
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PMID:Isolation and structure of the cytotoxic cycloheptapeptide phakellistatin 13. 1254 66

1. The metabolic pathway(s) of OGT 719, a novel nucleoside analogue in which galactose is covalently attached to the N1 of 5-fluorouracil (FU), have been investigated with (19)F-NMR spectroscopy in (1) the isolated perfused rat liver (IPRL) model, (2) normal rats, (3) rats bearing the HSN LV10 sarcoma, (4) nude mice xenografted with the human hepatoma HepG2 and (5) urine from patients. 2. The administration of OGT 719 results in the formation of small amounts of FU. IPRL experiments with OGT 719 in combination with asialofetuin, a natural asialoglycoprotein receptor (ASGP-r), suggest competitive binding of OGT 719 to the ASGP-r. 3. The data obtained in non-tumour rats also demonstrated an extremely low metabolization of OGT 719 into FU and alpha-fluoro-beta-alanine, the well-known major metabolite of FU. 4. A comparison of tumour extracts from rats bearing the HSN LV10 sarcoma treated with FU or OGT 719 showed the incorporation of FU into RNA in rats treated with FU but not in rats treated with OGT 719; nevertheless, the incorporation of FU into RNA was observed in the liver from rats treated with OGT 719. 5. In a human hepatoma xenografted to nude mice, both the OGT 719 and FU contents of the tumour were markedly higher than in the corresponding liver, suggesting a tumour-specific trapping of OGT 719 in hepatoma. 6. The metabolism of OGT 719 was also extremely low in patients. 7. In conclusion, the present study shows the value of (19)F-NMR for demonstrating for the first time that OGT 719 is a prodrug of FU although very poorly metabolized.
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PMID:Metabolism of a novel nucleoside analogue, OGT 719, in the isolated perfused rat liver model, in rats, in tumour models and in patients. 1263 46


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