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1.
PGA1 and PGA2 significantly depressed melanoma cell DNA synthesis and cell proliferation in a dose related fashion. Inhibition of DNA synthesis was rapid in onset (0.5–1 hr) and sustained (12 hr). This was not due to general cytotoxicity or depression of substrate uptake. Comparison with known cancer chemotherapeutic agent revealed PGA1 and PGA2 effectiveness on a molar basis exceeded that of Adriamycin, cyclophosphamide and hydroxyurea. Actinomycin D, Mutamycin and 5-fluorouracil were more potent than PGA1 and PGA2 but consideration of their toxicities may outweigh this point. The findings suggest that the A series prostaglandins or their analogs may be efficacious in cancer chemotherapy.  相似文献   

2.
The synthesis of several novel 11-substituted prostaglandins has been achieved from PGA2 methyl ester from the marine coral . The configuration of the substituents at position 11 is based on the nuclear magnetic resonance properties.  相似文献   

3.
The p-nitrophenacyl esters of a number of closely related and isomeric prostaglandins were resolved by HPLC on a microparticulate silica gel column (Zorbax-Sil ®, DuPont). Ten F-series prostaglandin analogs, eight E-series prostaglandin analogs, the isomeric 15(R)- and 15(S)-methyl prostaglandins of the E- and F-series and, lastly, PGA2 and PGB2 were chromatographed under conditions generating 2,000 to 7,000 theoretical plates. Conditions are described for quantitative conversion of prostaglandins to p-nitrophenacyl esters in less than 6 minutes at room temperature. Linear peak height and peak area plots were obtained for in-situ esterified PGE2 p-nitrophenacyl ester over the range of 0.4 – 3.1 μg. The lower limit of detection of this ester is about 1 ng. A linear relationship is observed between silica gel TLC 1/Rf values and HPLC retention times as predicted by theory.  相似文献   

4.
We have recently reported that cartilage has two sites for prostaglandin (PG) action. One site (S1) is stimulated by PGA1, PGE1 and PGF and elevates tissue cyclic 3′5′adenosine monophosphate (cAMP). A second site (S2) is activated by PGA1 (but not PGE1 or PGF) and inhibits the synthesis of cartilage macromolecules. The present study is an investigation of the effects of PGB1 on embryonic chicken cartilage chondromucoprotein synthesis in vitro. PGB1 was found to inhibit chondromucoprotein synthesis with an apparent affinity for S2 which was similar to that of PGA1. The maximal inhibition produced by PGB1 was, however, approximately one-half the maximal inhibition caused by PGA1. Studies of the combined effects of PGB1 and PGA1 were consistent with the hypothesis that both classes of prostaglandins act at a common site (S2) with about equal affinity but that PGB1 has a lower intrinsic activity than PGA1. Similar studies of the combined effects of PGE1 or PGF with PGA1 indicate that neither PGE1 nor PGF binds significantly to S2. An independent effect of PGB1 to activate S1 and elevate tissue cAMP was also found.  相似文献   

5.
The present study investigated the effect of prostaglandins (PG) on the in vitro production of polyclonal IgG and IgM by pokeweed mitogen- stimulated normal human peripheral mononuclear cells. Concentrations of PGE1 and PGA1 in excess of 10−6M were suppressive. PGE2 and PGs of the F series were less effective and significant suppression was seen in concentrations greater than 10−3M. Indomethacin added to cell cultures did not enhance Ig production. This discrepancy between physiologic PG concentrations and the very large pharmacologic concentration necessary to suppress Ig synthesis in vitro makes the physiologic role of PG in the modulation of Ig synthesis questionable.  相似文献   

6.
The ability of various prostaglandins (PGs) to affect the in vitro anamnestic immune response of keyhole limpet hemocyanin (KLH)-primed rabbit popliteal lymph node cells was investigated. Of the four PGs studied (PGA1, PGE2 and PGF), PGE1 was found to have a stimulatory effect, whereas PGA1, PGE2 and PGF were ineffective in stimulating or inhibiting the in vitro anamnestic response. Under the conditions studied, a 3.5-fold increase in antibody production was obtained in PGE1-treated, KLH-stimulated cultures. Maximum enhancement was obtained when 0.2 μg of PGE1 were added at the time of culture initiation and were allowed to remain in contact with the lymph node cells for 24 hours.  相似文献   

7.
Prostaglandin D2 was found to be a potent inhibitor of B-16 melanoma cell replication in vitro. The inhibition was dose-dependent between 3×10?9M and 3×10?6M (IC50~ 0.3 μM after 6 days). On a molar basis, PGD2 was a better inhibitor than PGA2 or 16,16-dimethyl-PGE2-methyl ester (di-M-PGE2) and in higher concentrations (10?6?10?7M), comparable to retinoic acid. In higher concentrations, PGD2 inhibited DNA, RNA and protein synthesis. The B-16 melanoma cell line which we used synthesized arachidonic acid metabolites which comigrated with PGA2, PGD2, PGE2 and PGF on a thin layer chromatography system.  相似文献   

8.
This paper reports the synthesis of 11-dehydrothromboxane B2 methyl ester (II), 15-dehydrothromboxane B2 methyl ester (III), 15-dehydro-13,14-dihydrothromboxane B2 (XII) and 2,3-dinorthromboxane B2 methyl ester (XV). These compounds, as their free acids, have been reported to be thromboxane metabolites.  相似文献   

9.
《Inorganica chimica acta》1988,142(2):229-234
An improved synthesis of VO(CysOCH3)2, (CysOCH3  the anion of cysteine methyl ester), is reported, as is an analogous preparation of VO(CysOCH2CH3)2, (CysOCH2CH3  the anion of cysteine ethyl ester). These are the first two examples of isolated vanadium-cysteine compounds. The oxidation of VO(CysOCH3)2 in DMSO is a reversible one electron change at 0.24 V versus SCE followed by a rapid chemical reaction which produces a stable vanadium(V) species. This species is reduced back to the vanadium(IV) complex at −1.30 V. The electrochemistry of VO(Cys-OCH2CH3)2 is nearly identical to that of the methyl ester compound.  相似文献   

10.
Abstract

In the past few years interest in the synthesis and biological properties of acyclic nucleosides has been generated based largely upon the development of acyclovir [9-[(2-hydroxyethoxy)methyll guanine, 1a] as an antiviral agent for the treatment of certain herpesvirus infections. The literature in the area covers a variety of different heterocycles, a variety of different side chains, and spans research that is strictly synthetic to research that is strictly biological. Two compounds, 9-[(2-hydroxy-l-(hydroxymethyl)ethoxy)methyl] guanine (1b) and 9-(S)-(2,3-dihydroxypropyl)adenine (2), have received the most attention, but many others have been made.  相似文献   

11.
The synthesis of ((±)-16-thioketal and 16-keto PGE2 methyl ester ( and ) is herein described.  相似文献   

12.
A rabbit lung preparation, perfused in vitro, was used to examine pulmonary metabolism of prostaglandin A1 (PGA1) and to compare the vasoconstrictor actions of PGA1, prostaglandin F (PGF) and angiotensin II. PGF caused significantly more, and angiotensin II significantly less, vasoconstriction than did an equimolar concentration of PGA1. Of three likely PGA1 metabolites only 15-keto-PGA1 had any significant vasoconstrictor action. Furosemide and aminophylline (10?3 M) reduced PGA1, PGF or angiotensin II-induced vasoconstruction. Diphloretin phosphate potentiated the vascular effect of angiotensin II. Furosemide (10?3 M) and DPP (9.5 × 10?6 M) significantly reduced pulmonary metabolism of PGA1 while aminophylline (10?3 M) had no effect on this process. Perfusion of the lungs with a hypoxic medium had no effect on PGA1 metabolism.  相似文献   

13.
The p-nitrophenacyl esters of a number of closely related and isomeric prostaglandins were resolved by HPLC on a microparticulate silica gel column (Zorbax-Sil®, DuPont). Ten F-series prostaglandin analogs, eight E-series prostaglandin analogs, the isomeric 15(R)- and 15(S)- methyl prostaglandins of the E- and F-series and, lastly, PGA2 and PGB2 were chromatographed under conditions generating 2,000 to 7,000 theoretical plates. Conditions are described for quantitative conversion of prostaglandins to p-nitrophenacyl esters in less than 6 minutes at room temperature. Linear peak height and peak area plots were obtained for esterified PGE2 p-nitrophenacyl ester over the range of 0.4 – 3.1 μg. The lower limit of detection of this ester is about 1 ng. A linear relationship is observed between silica gel TLC 1/Rf values and HPLC retention times as predicted by theory.  相似文献   

14.
The isolation, structure elucidation, total synthesis, and biological activity of PGF2α 15-methyl ether methyl ester are described.  相似文献   

15.
For use as the internal standards in a quantitative analysis of natural jasmonic acid (JA) and methyl jasmonate (JAMe) by gas chromatography-mass spectrometry-selected ion monitoring, (±)-2-(2,3–2H2)JA and its methyl ester, (±)-2-(2,3–2H2)JAMe, were efficiently prepared from 2-(2–pentyl)-2-cyclopentenone through catalytic semi-deuteriogenation of acetylenic intermediates with deuterium gas in pyridine.  相似文献   

16.
The cyclopentenone prostaglandin (cyPG) PGA1 displays potent anti-proliferative and anti-inflammatory effects. Therefore, PGA1 derivatives are being studied as therapeutic agents. One major mechanism for cyPG action is the modification of protein cysteine residues, the nature of the modified proteins being highly dependent on the structure of the cyPG. Biotinylated cyPGs may aid in the proteomic identification of cyPG targets of therapeutic interest. However, for the identified targets to be relevant it is critical to assess whether biotinylated cyPGs retain the desired biological activity. Here we have explored the anti-inflammatory, anti-proliferative and cell stress-inducing effects of a biotinylated analog of PGA1 (PGA1-biotinamide, PGA1-B), to establish its validity to identify cyPG–protein interactions of potential therapeutic interest. PGA1 and PGA1-B displayed similar effects on cell viability, Hsp70 and heme oxygenase-1 induction and pro-inflammatory gene inhibition. Remarkably, PGA1-B did not activate PPAR. Therefore, this biotinylated analog can be useful to identify PPAR-independent effects of cyPGs. Protein modification and subcellular distribution of PGA1-B targets were cell-type-dependent. Through proteomic and biochemical approaches we have identified a novel set of PGA1-B targets including proteins involved in stress response, protein synthesis, cytoskeletal regulation and carbohydrate metabolism. Moreover, the modification of several of the targets identified could be reproduced in vitro. These results unveil novel interactions of PGA1 that will contribute to delineate the mechanisms for the anti-proliferative and metabolic actions of this cyPG.  相似文献   

17.
Abstract

Several 4-substituted-1-β-D-ribofuranosyl-3-hydroxypyrazoles were prepared as structural analogs of pyrazofurin. Glycosylation of the TMS derivative of ethyl 3(5)-hydroxypyrazole-4-carboxylate (3) with 1-0-acetyl-2,3,5-tri-0-benzoyl-D-ribofuranose in the presence of TMS-triflate gave predominantly ethyl 3-hydroxy-1-(2,3,5-tri-0-benzoyl-β-D-ribofuranosyl)pyrazole-4-carboxylate (4a), which on subsequent ammonolysis furnished 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-carboxamide (5). Benzylation of 4a with benzyl bromide and further ammonolysis gave 3-benzyloxy-1-β-D-ribofuranosylpyrazole-4-carboxamide (8a). Catalytic (Pd/C) hydrogenation of 8a afforded yet another high yield route to 5. Saponification of the ester function of ethyl 3-benzyloxy-1-β-D-ribofuranosylpyrazole-4-carboxylate (7b) gave the corresponding 4-carboxylic acid (6a). Phosphorylation of 8a and subsequent debenzylation of the intermediate 11a gave 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-carboxamide 5′-phosphate (11b). Dehydration of 3-benzyloxy-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)pyrazole-4-carboxamide (8b) with POCl3 provided the corresponding 4-carbonitrile derivative (10a), which on debenzylation with Cl3SiI gave 3-hydroxy-1-(2,3,5-tri-0-acetyl-β-D-ribofuranosyl)pyrazole-4-carbonitrile (13). Reaction of 13 with H2S/pyridine and subsequent deacetylation gave 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-thiocarboxamide (12b). Similarly, treatment of 13 with NH2OH afforded 3-hydroxy-1-β-D-ribofuranosylpyrazole-4-carboxamidoxime (14a), which on catalytic (Pd/C) hydrogenation gave the corresponding 4-carboxamidine derivative (14b). The structural assignment of these pyrazole ribonucleosides was made by single-crystal X-ray analysis of 6a. None of these compounds exhibited any significant antitumor or antiviral activity in cell culture.  相似文献   

18.
The crystal and molecular structure of prostaglandin A1 (PGA1) has been determined by X-ray diffraction. (Space group P212121, a = 18.10A?A, b = 21.09A?A, c = 5.42, Z = 4). Comparison of the structure of PGA1 with that of PGF (determined previously as the tribromobenzoate) indicates significant differences in the relative intramolecular side chain orientations. However, conformation and torsional angles within each side chain of PGA1 are retained with little or no change in comparison with PGF, indicating the presence of the C15-bromobenzoate groups in the latter have had little effect in altering internal side chain conformation in the solid state. The overall differences in relative side chain orientation in PGA1 are attributable to chemical and conformational changes in the substituted cyclopentane moiety (C8-C12).  相似文献   

19.
Since the renal cortex has recently been shown to be a major site of prostaglandin A1 (PGA1) metabolism, studies were undertaken to isolate and characterize the major metabolites. Homogenates of rabbit cortex (500g) were incubated with 3H-PGA1 (50mg) in the presence of NAD+ (50mg). Acidic lipid extracts were subjected to linear gradient silicic acid chromatography. Six radioactive peaks were recovered, of which peak 4 was unconverted PGA1. The major metabolites (1,3) were further subjected to reversed phase partition chromatography and TLC with and without silver nitrate. Three PGA1 analogs were then synthesized via oxidation of the secondary alcohol group at C-15 by manganese dioxide (15-keto-PGA1). The second compound was synthesized by hydrogenation of 15-keto-PGA1 (15-keto 13, 14-dihydro PGA1). The third compound (13, 14-dihydro PGA1) was obtained by direct catalytic hydrogenation of PGA1. Purification of these substances were achieved by a combination of silicic acid and thin layer chromatography. It was found that metabolite 1 cochromatographed on TLC (AgNO3) with synthesized 15-keto 13, 14-dihydro PGA1. Both compounds were 100 times less potent than PGA1 in lowering rat blood pressure. Metabolite 3 cochromatographed on TLC (AgNO3) with synthesized 13, 14-dihydro PGA1. Both were as potent as PGA1 in lowering rat blood pressure. Metabolites 1 and 3 absorbed UV at 221 nm but not at 280 nm following alkali treatment. These studies suggest that rabbit renal cortex metabolizes PGA1 to what appears to be biologically active 13, 14-dihydro PGA1 and biologically inactive 15-keto 13, 14-dihydro PGA1. It remains possible that the hypotensive effect of PGA1 is the result of its conversion to its biologically active 13, 14-dihydro derivative.  相似文献   

20.
Summary Lipase fromCandida cylindracea was coupled with polyethylene glycol(PEG). In contrast to the previously used lipase fromPseudomonas fluorescens, the modified lipase catalyzed the ester synthesis in benzene at 25°C from short-chain alcohols and - or -substituted carboxylic acid. Using the modified lipase, following esters were synthesized; pentyl -methylpentanate, methyl benzoate, and methyl retinoate.  相似文献   

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