Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “bioactive compound”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,603 records · Page 89Linked to original sources
PubMed2005

Biosynthesis pathways for deoxysugars in antibiotic-producing actinomycetes: isolation, characterization and generation of novel glycosylated derivatives.

Many bioactive natural products synthesized by actinomycetes are glycosylated compounds in which the appended sugars contribute to specific interactions with their biological target. Most of these sugars are 6-deoxyhexoses, of which more than 70 different forms have been identified, and an increasing number of gene clusters involved in 6-deoxyhexoses biosynthesis are being characterized from antibiotic-producing actinomycetes. Novel glycosylated compounds have been generated by modifying natural deoxysugar biosynthesis pathways in the producer organisms, and/or the simultaneous expression in these strains of selected deoxysugar biosynthesis genes from other strains. Non-producing strains endowed with the capacity to synthesize novel deoxysugars through the expression of engineered deoxysugar biosynthesis clusters can also be used as alternative hosts. Transfer of these deoxysugars to a multiplicity of aglycones relies upon the existence of glycosyltransferases with an inherent degree of 'relaxed substrate specificity'. In this review, we analyze how the knowledge coming out from isolation and characterization of deoxysugar biosynthesis pathways from actinomycetes is being used to produce novel glycosylated derivatives of natural products.

Actinobacteria↗
PubMed2005

Enzymatic formation of prostamide F2alpha from anandamide involves a newly identified intermediate metabolite, prostamide H2.

Prostaglandin F2alpha 1-ethanolamide (prostamide F2alpha) is a potent ocular hypotensive agent in animals and represents a new class of fatty acid amide compounds. Accumulated evidence indicated that anandamide, an endogenous bioactive ligand for cannabinoid receptors, may serve as a common substrate to produce all prostamides, including prostamide F2alpha. After incubation of anandamide with cyclooxygenase 2 (COX-2), the reaction mixture was profiled by HPLC and an intermediate metabolite was discovered and characterized as a cyclic endoperoxide ethanolamide using HPLC-tandem mass spectrometry. Formation of prostamide F2alpha was also demonstrated when the intermediate metabolite was isolated and incubated with prostaglandin F synthase (PGF synthase). These results suggest that the biosynthesis of prostamide F2alpha proceeds in two consecutive steps: oxidation of anandamide to form an endoperoxide intermediate by COX-2, and reduction of the endoperoxide intermediate to form prostamide F2alpha by PGF synthase. This endoperoxide ethanolamide intermediate has been proposed as prostamide H2.

Arachidonic Acids↗
PubMed2006

Identification of a peptide mimic of bioactive gibberellins with affinity to GA 2-oxidase.

Previously we reported the first example of peptide mimics of a small hydrophobic molecule, a phytohormone gibberellin. The second peptide mimic of gibberellin has been identified from random peptide libraries by its affinity to a type of catalyzing enzyme of gibberellins, which specifically recognizes bioactive gibberellins. These results suggest that even hydrophobic compounds can be mimicked by peptides.

Catalysis↗
PubMed2003

Inhalation exposure of rats to asphalt fumes generated at paving temperatures alters pulmonary xenobiotic metabolism pathways without lung injury.

Asphalt fumes are complex mixtures of various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). PAHs require bioactivation by the cytochrome P-450 monooxygenase system to exert toxic/carcinogenic effects. The present study was carried out to characterize the acute pulmonary inflammatory responses and the alterations of pulmonary xenobiotic pathways in rats exposed to asphalt fumes by inhalation. Rats were exposed at various doses and time periods to air or to asphalt fumes generated at paving temperatures. To assess the acute damage and inflammatory responses, differential cell counts, acellular lactate dehydrogenase (LDH) activity, and protein content of bronchoalveolar lavage fluid were determined. Alveolar macrophage (AM) function was assessed by monitoring generation of chemiluminescence and production of tumor necrosis factor-alpha and interleukin-1. Alteration of pulmonary xenobiotic pathways was determined by monitoring the protein levels and activities of P-450 isozymes (CYP1A1 and CYP2B1), glutathioneS-transferase (GST), and NADPH:quinone oxidoreductase (QR). The results show that acute asphalt fume exposure did not cause neutrophil infiltration, alter LDH activity or protein content, or affect AM function, suggesting that short-term asphalt fume exposure did not induce acute lung damage or inflammation. However, acute asphalt fume exposure significantly increased the activity and protein level of CYP1A1 whereas it markedly reduced the activity and protein level of CYP2B1 in the lung. The induction of CYP1A1 was localized in nonciliated bronchiolar epithelial (Clara) cells, alveolar septa, and endothelial cells by immunofluorescence microscopy. Cytosolic QR activity was significantly elevated after asphalt fume exposure, whereas GST activity was not affected by the exposure. This induction of CYP1A1 and QR with the concomitant down-regulation of CYP2B1 after asphalt fume exposure could alter PAH metabolism and may lead to potential toxic effects in the lung.

Animals↗
PubMed2001

Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death.

Stress conditions and proinflammatory cytokines activate the c-Jun NH2-terminal kinase (JNK), a member of the stress-activated group of mitogen-activated protein kinases (MAPKs). We recently demonstrated that inhibition of JNK signaling with the use of the islet-brain (IB) 1 and 2 proteins prevented interleukin (IL)-1beta-induced pancreatic beta-cell death. Bioactive cell-permeable peptide inhibitors of JNK were engineered by linking the minimal 20-amino acid inhibitory domains of the IB proteins to the 10-amino acid HIV-TAT sequence that rapidly translocates inside cells. Kinase assays indicate that the inhibitors block activation of the transcription factor c-Jun by JNK. Addition of the peptides to the insulin-secreting betaTC-3 cell line results in a marked inhibition of IL-1beta-induced c-jun and c-fos expression. The peptides protect betaTC-3 cells against apoptosis induced by IL-1beta. All-D retro-inverso peptides penetrate cells as efficiently as the L-enantiomers, decrease c-Jun activation by JNK, and remain highly stable inside cells. These latter peptides confer full protection against IL-1beta-induced apoptosis for up to 2 weeks of continual treatment with IL-1beta. These data establish these bioactive cell-permeable peptides as potent pharmacological compounds that decrease intracellular JNK signaling and confer long-term protection to pancreatic beta-cells from IL-1beta-induced apoptosis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

[Isolation and structural elucidation of a bioactive saponin from tubers of Bolbostemma paniculatum].

OBJECTIVE: To study the bioactive constituents from tubers of Bolbostemma paniculatum. METHOD: Compounds were isolated by extraction and partition as well as several-chromatographic techniques guided with Pyricularia oryzae bioassay method. Their structures were determined on the basis of spectral analysis and chemical evidence. RESULT: Bisdesmoside (I) was isolated as active compound causing morphological abnormality of Pyncularia oryzae mycelia and elucidated as 3-0-alpha-L-arabinopyranosyl (1-->2)-beta-D-glucopyranosyl-bayogenin-28-O-beta-D-xylopyranosyl (1-->3)-alpha-L-rhamnopyranosyl (1-->2)-alpha-L-arabinopyranoside. CONCLUSION: I is a new natural product and exhibited significant cytotoxicity against cancer cell lines K-562 and BEL-7402, but no hemolytic activity to rabbit erythrocytes.

Animals↗
PubMed1994

Synthesis and cytotoxic evaluation of some cyclic arylidene ketones and related oximes, oxime esters, and analogs.

A number of arylidene derivatives of alicyclic ketones and some corresponding oximes, oxime esters, and related compounds were prepared as candidate cytotoxic agents. All of the compounds were evaluated against murine L1210 lymphoid leukemia cells. In general, cytotoxicity was greatest with the alpha,beta-unsaturated ketones and diminished with the oximes, and the oxime esters had little or no activity in this screen. When the same compounds were examined in both the in vitro L1210 and P388 leukemia screens, in the majority of cases the L1210 cells were more sensitive to these derivatives. Over half of the compounds prepared were evaluated against approximately 55 human tumors in vitro and showed selective toxicity toward one or more groups of neoplastic diseases, particularly leukemia. Some correlations between structure and bioactivity were discerned. The cytotoxicity screening and stability studies of representative compounds suggested that the ketones, oximes, and oxime esters were stable under the conditions of bioevaluation. X-ray crystallography of four representative compounds revealed structural features associated with cytotoxicity which may be considered in the design of future candidate cytotoxins.

Animals↗
PubMed1990

Glutathione-dependent bioactivation of xenobiotics: implications for mutagenicity and carcinogenicity.

Glutathione conjugate formation is now recognized as an important bioactivation mechanism for several classes of mutagenic and carcinogenic compounds. For example, dihalomethanes, 1,2-dihaloethanes, and 1,2,3-trihalopropanes are metabolized to glutathione conjugates that are direct-acting, i.e., that require no further enzymatic processing, and that are cytotoxic or mutagenic, or both. Nephrotoxic and nephrocarcinogenic haloalkenes are metabolized by a multistep pathway that involves hepatic glutathione S-conjugate formation, conversion of the glutathione S-conjugates to cysteine S-conjugates, translocation of the cysteine S-conjugates to the kidney, and bioactivation by renal cysteine conjugate beta-lyase. Fluoroalkene-derived conjugates are cytotoxic, whereas chloroalkene-derived conjugates are both cytotoxic and mutagenic. Beta-Lyase-dependent bioactivation may account for the observed nephrocarcinogenicity of hexachlorobutadiene, tetrachloroethylene, and trichloroethylene. Finally, glutathione conjugate formation has been implicated in the mutagenicity of Trp-P-2 and N-OH-Trp-P-2 and in the DNA damage produced by 1-methyl-4-phenyl-5-nitroimidazole. Glutathione may also play a role in the toxicity or action of several cancer chemotherapeutic agents, including N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-methylformamide, cyclophosphamide, neocarzinostatin, and bleomycin.

Animals↗
PubMed1992

Flexibilized gelatin film-based artificial skin model: II. Release kinetics of incorporated bioactive molecules.

Any delivery system for bioactive molecules should have the ability to release the compound in question in a reproducible and predictable way over a certain period. For artificial skin models that are designed to enhance healing by the use of growth factors, this requirement poses another problem: the design of a delivery method that can provide a realistic assessment of the release kinetics. This means that the design should "mimic" conditions encountered in an open wound, i.e., only a certain part of the film can face the wound, from which it can absorb wound fluid that will dissolve the incorporated bioactive molecule and bring it to the open wound. Such a system has been developed and the release of 125I-labelled insulin, incorporated into flexibilized gelatin films, has been determined. The details of this study follow.

Collagenases↗
PubMed2005

Hypothesis of potential active components in Angelica sinensis by using biomembrane extraction and high performance liquid chromatography.

The screening and analysis of bioactive components in traditional Chinese medicines (TCMs) is very important not only for the quality control of crude drugs but also for elucidating the therapeutic principle. In this study, a method for screening potential active components from TCMs was developed by using biomembrane extraction and high performance liquid chromatography. Based on the methodology, aqueous extract of Angelica sinensis (WEAS) was used, and four compounds were detected by HPLC in the desorption eluate of red cell membrane extraction for WEAS. The compounds were identified as ferulic acid, ligustilide, senkyunolide H and senkyunolide I based on their UV, MS and NMR spectra. Actually, ferulic acid and ligustilide are considered as major active components in Angelica sinensis. Therefore, this method may be applied to predict the potential bioactivities of multiple compounds in TCMs simultaneously.

Angelica↗
PubMed2005

The stimulatory role of human cytochrome b5 in the bioactivation activities of human CYP1A2, 2A6 and 2E1: a new cell expression system to study cytochrome P450 mediated biotransformation.

Cytochrome b(5) (b(5)) is increasingly recognized to be of importance for specific cytochrome P450 (CYP) activities. We developed human b(5)/CYP-competent mutagenicity tester bacteria to study the role of b(5) in the bioactivation activity of human CYP. These new tester bacteria were derived from the previously engineered human CYP-competent Escherichia coli K12 tester strain MTC, containing a bi-plasmid system for the co-expression of a specific CYP form (CYP1A2, 2A6 or 2E1) with human b(5), and human NADPH cytochrome P450 reductase (RED), resulting in the strain BTC-b(5)-1A2, BTC-b(5)-2A6 and BTC-b(5)-2E1, respectively. The relative content of b(5) with CYP and RED in these three BTC-b(5)-CYP strains demonstrated physiologically relevant co-expression levels and typical CYP-specific activities could be determined with their specific chemical probes. These strains were applied in mutagenicity assays along with their corresponding b(5)-void strains to determine the effect of b(5) on the CYP1A2-, CYP2A6- and CYP2E1-mediated bioactivation of several promutagens. For CYP1A2, of the 5 compounds tested [2-aminoanthracene (2AA), 1-aminopyrene, 6-aminochrysene, 2-amino-3-methylimidazo(4,5-f)quinoline and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)], only the mutagenicity of 2AA was slightly increased ( approximately 1.5-fold) in the presence of b(5). The CYP2E1- and CYP2A6-dependent mutagenicity of N-nitrosodiethylamine increased approximately 3- and 23-fold, respectively when the bacteria contained b(5). The CYP2A6-mediated mutagenicity of NNK increased approximately 9-fold when co-expressed with b(5). The stimulatory effect of b(5) on the bioactivation of N-nitrosodi-n-propylamine was most striking. The mutagenicity of this procarcinogen was completely dependent on the co-expression of b(5) with CYP2A6 or CYP2E1. This demonstrates the prominent role of b(5) in the bioactivation of this carcinogen.

Aryl Hydrocarbon Hydroxylases↗
PubMedDate not supplied

Anticancer activity of tirucallane triterpenoids from Amoora dasyclada.

A new tetranortriterpene 3alpha-acetoxy-24,25,26,27-tetranortirucalla-7-ene-23(21)-lactone (3), and eleven other compounds were isolated from the twigs of Amoora dasyclada. The structure of compound 3 was identified on the basis of spectroscopic data, and the bioactive experiments of 1 and 3-5 against AGZY 83-a (human lung cancer cells) and SMMC-7721 (human liver cancer cells) are documented. Among them, compound 5 exhibited a strong activity against SMMC-7721.

Animals↗
PubMed2005

Controlled release from fibers of polyelectrolyte complexes.

Controlled release systems for delicate compounds, such as proteins, often suffer the drawbacks of decreased bioactivity and low encapsulation efficiency. This study introduces the concept of producing drug-loaded fibers from interfacial polyelectrolyte complexation. Chitosan-alginate fibers were produced by pulling from the interface between two polyelectrolyte solutions at room temperature. Depending on the component properties, the release time of encapsulated components from these fibers can range from hours to weeks. Dexamethasone was completely released within 2 h, whereas charged compounds such as BSA, PDGF-bb, and avidin showed sustained release for 3 weeks. The fibers were able to release PDGF-bb in a steady fashion for over 3 weeks without an initial burst. Furthermore, the bioactivity of PDGF-bb was retained over this period. Release kinetics could be controlled by the inclusion of heparin, which contains specific binding sites for various growth factors. By varying the alginate/heparin ratios in the anionic polyelectrolyte solution, the release of PDGF-bb could be significantly altered. In this study, interfacial polyelectrolyte complexation has been demonstrated to be a promising technique for producing drug-loaded fibers with high encapsulation efficiency, sustained release kinetics, and capacity to retain the bioactivity of the encapsulants.

Alginates↗
PubMed2003

Bioassay-guided isolation of epiquinamide, a novel quinolizidine alkaloid and nicotinic agonist from an Ecuadoran poison frog, Epipedobates tricolor.

Analytical HPLC fractionation, combined with an off-line 96-well fluorescent bioassay screen, has been developed and used for the separation and screening of a natural product extract. This method was used to guide the isolation of a novel quinolizidine alkaloid from the methanolic skin extracts of an Ecuadoran frog, Epipedobates tricolor. The structure was determined on the basis of MS, IR, and NMR analysis as (1R,10R)-1-acetamidoquinolizidine (alkaloid 196). We have named this compound epiquinamide, reflecting its origin and structure. The activity of the isolated compound was determined in five cell lines expressing various nicotinic acetylcholine receptor subtypes. The bioactivity of epiquinamide was evaluated on the basis of membrane potential fluorescence and was found to be beta2 selective. This compound represents a new structural class of nicotinic agonists and a potential lead compound for the development of new therapeutics and pharmacological probes for nicotinic receptors. The off-line screening technique was found to be very sensitive for the detection of compounds active at nicotinic receptors.

Alkaloids↗
PubMed2007

Electrophilic chemistry related to skin sensitization. Reaction mechanistic applicability domain classification for a published data set of 106 chemicals tested in the mouse local lymph node assay.

This article presents an overview of electrophilic reaction mechanisms relevant to skin sensitization, with reference to a published skin sensitization test data set for 106 chemicals. Where appropriate to aid the interpretation, additional data on a small number of further compounds are also discussed. It is shown that there is a close correspondence in the way differences and similarities in skin sensitization potency of chemicals relate to differences and similarities in their physical organic chemistry and electrophilic reaction mechanistic chemistry. The 106 chemicals are classified into their reaction mechanistic applicability domains, and reactivity-sensitization trends are analyzed for each domain: the Michael acceptor and pro-Michael acceptor electrophile domain; the SNAr electrophile domain; the SN2 electrophile domain; the Schiff base electrophile domain; the acyl transfer electrophile domain; and the non-electrophilic non-pro-electrophilic domain. The last of these domains should be populated mainly by non-sensitizers. Classification of 87 of the 106 compounds, using these domains, was straightforward. In most of the domains and subdomains where there are sufficient compounds, clear trends can be seen, in conformity with the Relative Alkylation Index (RAI) model, between sensitization potential and reactivity/hydrophobicity. Of the remaining 19 compounds, 7 are alpha-X-methyl-gamma-lactones that on the basis of published organic chemistry studies and guinea pig sensitization data can be classed as pro-Michael acceptors by elimination of HX but that are mostly negative in the LLNA, indicating a difference in bioactivation capabilities between mice and guinea pigs. The other 12 compounds, whose chemistry was not immediately obvious, were found after further analysis and literature research to fit into appropriate mechanistic domains that rationalize their skin sensitizing properties.

Animals↗
PubMed2002

Evaluation of genotoxicity of captan, maneb and zineb in the wing spot test of Drosophila melanogaster: role of nitrosation.

The wing spot test in Drosophila melanogaster is a suitable system for the analysis of genotoxic activity of compounds that need metabolic transformation to render them active. We have analysed the genotoxicity of three fungicides for which it was reported that the metabolic processes taking place in vivo may determine their activity. The compounds analysed are captan, maneb, zineb and ethylenethiourea (ETU) (a metabolic derivative of ethylenebisdithiocarbamates like maneb and zineb). We have also evaluated the ability of ETU to form genotoxic derivatives in vivo analysing this compound in combined treatments with sodium nitrite. Both standard and high bioactivation NORR strains have been used. Captan, usually considered a mutagen in vitro but a non-mutagen in vivo, gave negative results in the wing spot test with both crosses. Positive results were obtained for maneb in the standard cross and for ETU in both the standard and the high bioactivation cross. The genotoxicities of maneb and ETU were higher when treatments were made on media in which nitrosation is favoured. A low absorption of the fungicide and an inefficient availability of the compound in the target may explain negative results obtained with zineb in both crosses. The results obtained in this study with the wing spot test demonstrate once again the suitability of this in vivo assay, in which absorption, distribution and metabolism processes take place, for the evaluation of genotoxicity of compounds to which humans are exposed.

Animals↗
PubMed2004

Strategies for compound selection.

In-house pharmaceutical collections are no longer sufficient for sampling chemical spaces. As novel bioactive chemotypes are successfully identified by virtual and high -throughput screening, the ability to rapidly sift through large numbers of chemicals prior to acquisition or experiment is required. Strategies for compound selection include some of the following steps: 1.) database assembly ('in silico' inventory); 2a.) structural integrity verification (keep unique structures only); 2b.) limited exploration of alternative chemical representations for the uniques (stereoisomers, tautomers, ionization states); 3.) property and structural filtering (remove unwanted structures); 4.) 3D-structure generation (for virtual screening or 3D-based similarity); 5a.) clustering or statistical design for selection; 5b.) similarity-based selection (if bioactives are known); 5c.) receptor-based selection (if target binding site is known); 6.) add a random subset to the final list.

Cluster Analysis↗
PubMedDate not supplied

Comparison of the antigonadotropic activity of three GnRH antagonists (Nal-Glu, Antide and Cetrorelix) in a non-human primate model (Macaca fascicularis).

We compared the antigonadotropic activity of the GnRH antagonists Nal-Glu, Antide and Cetrorelix in a non-human primate model (Macaca fascicularis). Orchidectomized animals received a single subcutaneous injection at doses of 250 micrograms kg-1 (n = 4), 625 micrograms kg-1 (n = 4) and 1250 micrograms kg-1 (n = 3) of the compounds Nal-Glu ([Ac-D-Nal(2)1, D-4-Cl-Phe2, D-Pal3, Arg5, D-Glu(AA)6, D-Ala10]-GnRH), Antide (Nal-Lys, [Ac-D-Nal1, D-4-Cl-Phe2, D-Pal3, Nic-Lys5, D-Nic-Lys6, Ip-Lys8, D-Ala10]-GnRH) or Cetrorelix ([Ac-D-Nal1, D-4-Cl-Phe2, D-Pal3, D-Cit6, D-Ala10]-GnRH). Blood samples were collected before and 3, 6, 12, 24, 48, 72, and 96 h after GnRH antagonist administration. Serum was analysed for concentrations of bioactive LH and immunoactive LH and FSH. All three compounds decreased LH secretion within 3-12 h (P < 0.05) and FSH secretion within 12-48 h (P < 0.05) after injection. Major differences between the GnRH antagonists were observed with regard to the effective dose and duration of action. At a dose of 250 micrograms kg-1 Nal-Glu and Antide only transiently suppressed LH and FSH release, whereas Cetrorelix induced complete inhibition (P < 0.05) which lasted for the entire observation period. At a dose of 625 micrograms kg-1 Cetrorelix exhibited the longest duration of action and Nal-Glu the shortest. At the highest dose of 1250 micrograms kg-1 Nal-Glu, Antide and Cetrorelix markedly inhibited LH and FSH secretion throughout the entire study period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗