Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The new (20R)-22E-cholesta-4,22-diene-3,6-dione (1), along with three known 3-keto steroids were isolated from the deep-water Mediterranean scleractinian coral Dendrophyllia cornigera (2-4). Moreover, four known related 3-keto steroids were isolated from the sea grass Cymodocea nodosa (5-8). The structure elucidation of steroid 1 and the full NMR resonance assignments of all isolated metabolites were based on interpretation of their spectral data. All compounds are reported for the first time as metabolites of the investigated organisms. Compounds 2 and 3 showed significant cytotoxicity against lung cancer NSCLC-N6 cell line.
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PMID:3-Keto steroids from the marine organisms Dendrophyllia cornigera and Cymodocea nodosa. 1628 Jan 45

Almost all heat shock protein 90 inhibitors reported so far, which are natural product derivatives, have problems mainly with toxic side effects, and with bioavailability and solubility. In our earlier studies, we compared the steric conformational structures of substance P[6-11] with our substance P antagonists in silico, and used the diverse biological effects of these compounds as tools in our modeling and design studies for discovering antiproliferative drugs. Here, we present a new synthesized short peptide-derivative compound family that inhibits only the function of the tumor cell's heat shock protein 90 and selectively kills in vitro more cancer cells than normal cells. During the lead generation, we observed that the difference between the most effective inhibitors was only one residue or group that caused diverse effects in vitro on the studied cell lines. According to our in vivo experiments on nude mice bearing lung cancer xenografts, the inhibitors restrained tumor growth, but not caused overt toxicity. We undertook NMR spectroscopy studies to analyze the 3D molecular structural differences of our inhibitors that control their binding to the target molecule. In conclusion, we demonstrated the efficacy of new selective and small molecule anticancerogen heat shock protein 90 inhibitors with peptide nature, without in vivo toxicity on nude mouse xenograft model. Our results also shed light on the mechanism of anticancerogen action of some substance P antagonists and their derivatives.
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PMID:Novel nontoxic heat shock protein 90 inhibitors having selective antiproliferative effect. 1654 Mar 63

Transcriptomics provides the tool for deciphering gene expression networks, and proteomics links these networks to protein products. The third crucial partner is metabolomics, which defines the metabolic network(s) linked to gene expression. NMR and mass spectrometry enable the broad screen analysis of the metabolome and its transformation pathways, transcending classical targeted metabolic studies. These tools were combined to investigate the anticancer mechanisms of different selenium forms in human lung cancer cells. Using 2-D NMR and tandem-MS, we mapped perturbations of 13C labeling patterns in numerous metabolites induced by selenite and selenomethionine. This information was used to interpret selenite-induced changes in gene expression networks. Linking metabolic dysfunctions to altered gene expression profiles provided new insights into the regulatory network underlying the metabolic dysfunctions, enabled the assembly of discrete gene expression events into functional pathways, and revealed protein targets for proteomic analysis.
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PMID:Integrating metabolomics and transcriptomics for probing SE anticancer mechanisms. 1714 97

The applications of 'omics' (genomics, transcriptomics, proteomics and metabolomics) technologies in nutritional studies have opened new possibilities to understand the effects and the action of different diets both in healthy and diseased states and help to define personalized diets and to develop new drugs that revert or prevent the negative dietary effects. Several single nucleotide polymorphisms have already been investigated for potential gene-diet interactions in the response to different lipid diets. It is also well-known that besides the known cellular effects of lipid nutrition, dietary lipids influence gene expression in a tissue, concentration and age-dependent manner. Protein expression and post-translational changes due to different diets have been reported as well. To understand the molecular basis of the effects and roles of dietary lipids high-throughput functional genomic methods such as DNA- or protein microarrays, high-throughput NMR and mass spectrometry are needed to assess the changes in a global way at the genome, at the transcriptome, at the proteome and at the metabolome level. The present review will focus on different high-throughput technologies from the aspects of assessing the effects of dietary fatty acids including cholesterol and polyunsaturated fatty acids. Several genes were identified that exhibited altered expression in response to fish-oil treatment of human lung cancer cells, including protein kinase C, natriuretic peptide receptor-A, PKNbeta, interleukin-1 receptor associated kinase-1 (IRAK-1) and diacylglycerol kinase genes by using high-throughput quantitative real-time PCR. Other results will also be mentioned obtained from cholesterol and polyunsaturated fatty acid fed animals by using DNA- and protein microarrays.
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PMID:High-throughput functional genomic methods to analyze the effects of dietary lipids. 1716 68

Multinuclear Pt(II) complexes represent a novel class of antitumor agents. In this work, a dinuclear monofunctional Pt(II) complex {[cis-Pt(NH(3))(2)Cl](2)(4,4'-methylenedianiline)}(NO(3))(2) (1) was synthesized and characterized by (1)H NMR, electrospray mass spectrometry, and elemental analysis. The 2D [(1)H,(15)N] heteronuclear single quantum coherence NMR spectra of (15)N-labeled 1 revealed that the cationic core of this water-soluble complex hardly hydrolyzes in aqueous solution and reacts very slowly with glutathione. Hydrolysis appears not to be an essential step for the formation of Pt-guanosine-5'-monophosphate (5'-GMP) or Pt-DNA adducts because the complex can react readily with 5'-GMP and partially transform B-DNA into its Z form. Such properties are desired to achieve the goal of enhancing cytotoxicity and lowering side effects of Pt(II) complexes. In fact, complex 1 is highly cytotoxic against the murine leukemia (P-388) and the human non-small-cell lung cancer (A-549) cell lines, and it is more cytotoxic than cisplatin at most concentrations tested.
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PMID:A dinuclear monofunctional platinum(II) complex with an aromatic linker shows low reactivity towards glutathione but high DNA binding ability and antitumor activity. 1733 97

A new compound and twelve known compounds were isolated from the ethyl acetate extract of the roots of Homonoia riparia Lour, which are used in folk medicine for treatment of hepatitis, bellyache and scald, by the method of silica gel column chromatography repeatedly with a gradient of PE-EtOAc, PE-Me2CO, CHCl3-Me2CO, CHCl3-MeOH. Their structures were identified as a new compound 1-oxo-aleuritolic acid (1), and twelve known compounds aleuritolic acid (2), 3-acetoxy-aleuritolic acid (3), taraxerone (4), taraxerol (5), methyl 3-acetoxy-12-oleanen-28-oate (6), 3-acetoxy-12-oleanen-28-ol (7), ursolic acid (8), lupenol (9), 3beta-acetoxy-lupenol (10), cleomiscosin A (11), chrysophanol (12), and gallic acid (13), which were obtained from this plant for the first time, by the spectroscopic techniques of NMR, HMBC, IR and MS, separately. Among the cytotoxicities evaluation of compounds 1 -3 towards AGZY 83-a (human lung cancer cells) and SMMC-7721 (human liver cancer cells) tumor cells was assayed by MTT methods with cis-dichlorodiamminoplatinum (DDP) used as positive control. Compound 2 exerted weak activity against AGZY 83-a with the IC50 value of 33.055 microg x mL(-1), while 1 and 3 showed no activity to these two cell lines.
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PMID:Chemical constituents from the roots of Homonoia riparia. 1752 Aug 29

Two new C(14) polyacetylenes dendrazawayne A(7) and dendrazawayne B (9) together with known C(13) polyacetylenes (2, 3), C(14) polyacetylenes (1, 4, and 8) and polyacetylene amides (5 and 6) were isolated from the roots of Dendranthema zawadskii. The structures of 7 and 9 were elucidated based on spectroscopic methods including 2D-NMR, HR-TOF-MS, IR, and UV. Compounds 1, 2, 3, 5, and 6 showed moderate activity against tumor cell lines (human small lung cancer cell line A549, melanoma SK-Mel-2, and mouse melanoma B16F1) with IC(50) values in the range of 7.4 - 30 microg/mL. Compounds 7 and 9, including other polyacetylenes, showed strong activity against the fungus Trichophyton (MIC: 5 - 10 microg/mL).
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PMID:Dendrazawaynes A and B, antifungal polyacetylenes from Dendranthema zawadskii (Asteraceae). 1769 Oct 57

Biologically active molecules, such as many peptides, serve as targeting vectors for radiopharmaceuticals based on 99mTc. Tripeptides can be suitable chelates and are easily and conveniently synthesized and linked to peptide targeting vectors through solid-phase peptide synthesis and form stable TcVO complexes. Upon complexation with [TcO]3+, two products form; these are syn and anti diastereomers, and they often have different biological behavior. This is the case with the approved radiopharmaceutical [99mTcO]depreotide ([99mTcO]P829, NeoTect) that is used to image lung cancer. [99mTcO]depreotide indeed exhibits two product peaks in its HPLC profile, but assignment of the product peaks to the diastereomers has proven to be difficult because the metal peptide complex is difficult to crystallize for structural analysis. In this study, we isolated diastereomers of [99TcO] and [ReO] complexes of several tripeptide ligands that model the metal chelator region of [99mTcO]depreotide. Using X-ray crystallography, we observed that the early eluting peak (A) corresponds to the anti diastereomer, where the Tc=O group is on the opposite side of the plane formed by the ligand backbone relative to the pendant groups of the tripeptide ligand, and the later eluting peak (B) corresponds to the syn diastereomer, where the Tc=O group is on the same side of the plane as the residues of the tripeptide. 1H NMR and circular dichroism (CD) spectroscopy report on the metal environment and prove to be diagnostic for syn or anti diastereomers, and we identified characteristic features from these techniques that can be used to assign the diastereomer profile in 99mTc peptide radiopharmaceuticals like [99mTcO]depreotide and in 188Re peptide radiotherapeutic agents. Crystallography, potentiometric titration, and NMR results presented insights into the chemistry occurring under physiological conditions. The tripeptide complexes where lysine is the second amino acid crystallized in a deprotonated metallo-amide form, possessing a short N1-M bond. The pKa measurements of the N1 amine (pKa approximately 5.6) suggested that this amine is rendered more acidic by both metal complexation and the presence of the lysine residue. Furthermore, peptide chelators incorporating a lysine (like the chelator of [TcO]depreotide) likely exist in the deprotonated form in vivo, comprising a neutral metal center. Deprotonation possibly mediates the interconversion process between the syn and anti diastereomers. The N1 amine group on non-lysine-containing metallopeptides is not as acidic (pKa approximately 6.8) and does not deprotonate and crystallize as do the metallo-amide species. Three of the tripeptide ligands (FGC, FSC, and FKC) were radiolabeled with 99mTc, and the individual syn and anti isomers were isolated for biodistribution studies in normal female nude mice. The main organs of uptake were the liver, intestines, and kidneys, with the FGC compounds exhibiting the highest liver uptake. In comparing the diastereomers, the syn compounds had substantially higher organ uptake and slower blood clearance than the anti compounds.
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PMID:MO tripeptide diastereomers (M=99/99mTc, Re): models to identify the structure of 99mTc peptide targeted radiopharmaceuticals. 1769 66

Mammalian IRPs (iron regulatory proteins), IRP1 and IRP2, are cytosolic RNA-binding proteins that post-transcriptionally control the mRNA of proteins involved in storage, transport, and utilization of iron. In iron-replete cells, IRP2 undergoes degradation by the ubiquitin/proteasome pathway. Binding of haem to a 73aa-Domain (73-amino-acid domain) that is unique in IRP2 has been previously proposed as the initial iron-sensing mechanism. It is shown here that recombinant IRP2 and the 73aa-Domain are sensitive to proteolysis at the same site. NMR results suggest that the isolated 73aa-Domain is not structured. Iron-independent cleavage of IRP2 within the 73aa-Domain also occurs in lung cancer (H1299) cells. Haem interacts with a cysteine residue only in truncated forms of the 73aa-Domain, as shown by a series of complementary physicochemical approaches, including NMR, EPR and UV-visible absorption spectroscopy. In contrast, the cofactor is not ligated by the same residue in the full-length peptide or intact IRP2, although non-specific interaction occurs between these molecular forms and haem. Therefore it is unlikely that the iron-dependent degradation of IRP2 is mediated by haem binding to the intact 73aa-Domain, since the sequence resembling an HRM (haem-regulatory motif) in the 73aa-Domain does not provide an axial ligand of the cofactor unless this domain is cleaved.
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PMID:Human iron regulatory protein 2 is easily cleaved in its specific domain: consequences for the haem binding properties of the protein. 1776 May 63

The skin of Bufo bufo gargarizans, originated from Bufo bufo gargarizans Cantor (Bufonidae), is widely used in traditional Chinese medicine for the treatment of hepatoma, lung cancer and etc. The preparation of the aqueous components has significant therapeutic effect against the digestive tract cancer. The water-soluble chemical constituents in the skin of Bufo bufo gargarizans were then investigated to make clear the active compounds. Six compounds were isolated and purified by recrystallization and column chromatography on silica gel and ODS, their structures were elucidated as 4-amido-3-hydroxymethyl-cyclooctylamidezotetra-alpha-furanone (I), bufogargarizanine C (II), bufothionine (III), dehydrobufotenine hydrobromide (IV), suberic acid (V) and succinic acid (VI) on the basis of physicochemical properties and spectral data (UV, IR, 1H NMR, 13C NMR and MS). Of the above compounds, compounds I and II are new compounds and named bufogargarizanine B and C, respectively.
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PMID:[Isolation and structure identification of chemical constituents from the skin of Bufo bufo gargarizans]. 1794 35


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