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 559 records · Page 31Linked to original sources
PubMed2005

Furocoumarins from grapefruit juice and their effect on human CYP 3A4 and CYP 1B1 isoenzymes.

Bioactive compounds present in grapefruit juice are known to increase the bioavailability of certain medications by acting as potent CYP 3A4 inhibitors. An efficient technique has been developed for isolation and purification of three furocoumarins. The isolated compounds have been tested for the inhibition of human CYP 1B1 isoform using specific substrates. Grapefruit juice was extracted with ethyl acetate (EtOAc) and the dried extract was loaded onto silica gel column chromatography. Further, column fractions were subjected to preparative HPLC to obtain three compounds. The purity of these compounds was analyzed by HPLC and structures were determined by NMR studies. The identified compounds, bergamottin, 6',7'-dihydroxybergamottin (DHB), and paradisin-A, were tested for their inhibitory effects on hydroxylase and O-dealkylase activities of human cytochrome P450 isoenzymes CYP 3A4 and CYP 1B1. Paradisin-A was found to be a potent CYP 3A4 inhibitor with an IC50 of 1.2 microM followed by DHB and bergamottin. All three compounds showed a substantial inhibitory effect on CYP 3A4 below 10 microM. Inhibitory effects on CYP 1B1 exhibited a greater variation due to the specificity of substrates. Paradisin A showed an IC50 of 3.56+/-0.12 microM for the ethoxy resorufin O-dealkylase (EROD) activity and 33.56+/-0.72 microM for the benzyloxy resorufin (BROD). DHB and bergamottin showed considerable variations for EROD and BROD activities with an IC50 of 7.17 microM and 13.86 microM, respectively.

Aryl Hydrocarbon Hydroxylases↗
PubMed2004

Facile synthesis of 4-substituted-4-aminopiperidine derivatives, the key building block of piperazine-based CCR5 antagonists.

4-Substituted-4-aminopiperidine is an interesting structural motif found in a number of bioactive compounds. An efficient and convenient method for the synthesis of 4-differently substituted-4-aminopiperidine derivatives was described, employing isonipecotate as a starting material and Curtius rearrangement as a key step. The alkylation of isonipecotate could introduce various substituents at the 4-position of the piperidine ring. With this key building block, we are able to efficiently synthesize piperazino-piperidine based CCR5 antagonist in a highly convergent manner free of using toxic reagents such as diethylaluminum cyanide. The concise synthesis of a potent bioavailable CCR5 antagonist as HIV-1 entry inhibitor, Sch-350634 (1) was accomplished in excellent yield using N'-Boc-4-methyl-4-aminopiperidine 5a as a smart building block. The new methodology provides a facile and practical access to the piperazino-piperidine amide analogs as HIV-1 entry inhibitors.

Alkylation↗
PubMed2005

QSAR for anti-RNA-virus activity, synthesis, and assay of anti-RSV carbonucleosides given a unified representation of spectral moments, quadratic, and topologic indices.

The unified representation of spectral moments, classic topologic indices, quadratic indices, and stochastic molecular descriptors show that all these molecular descriptors lie within the same family. Consequently, the same prior probability for a successful quantitative-structure-activity-relationship (QSAR) may be expected irrespective of which indices are selected. Herein, we used stochastic spectral moments as molecular descriptors to seek a QSAR using a database of 221 bioactive compounds previously tested against diverse RNA-viruses and 402 nonactive ones. The QSAR model thus obtained correctly classifies 90.9% of compounds in training. The model also correctly classifies a total of 87.9% of 207 compounds on additional external predicting series, 73 of them having anti-RNA-virus activity and 134 nonactive ones. In addition, all compounds were regrouped into five different subsets for leave-group-out studies: (1) anti-influenza, (2) anti-picornavirus, (3) anti-paramyxovirus, (4) anti-RSV/anti-influenza, and (5) broad range anti-RNA-virus activity. The model has retained overall accuracies of about 90% on these studies validating model robustness. Finally, we exemplify the practical use of the model with the discovery of compounds 124 and 128. These compounds presented MIC50 values=3.2 and 8 microg/mL against respiratory syncytial virus (RSV) respectively. Both compounds also have low cytotoxicity expressed by their Minimal Cytotoxic Concentrations >400 microg/mL for HeLa cells. The present approach represents an effort toward a formalization and application of molecular indices in bioorganic and medicinal chemistry.

Antiviral Agents↗
PubMed2006

Resveratrol--a boon for treating Alzheimer's disease?

Resveratrol, a red wine polyphenol, is known to protect against cardiovascular diseases and cancers, as well as to promote antiaging effects in numerous organisms. It also modulates pathomechanisms of debilitating neurological disorders, such as strokes, ischemia, and Huntington's disease. The role of resveratrol in Alzheimer's disease is still unclear, although some recent studies on red wine bioactive compounds suggest that resveratrol modulates multiple mechanisms of Alzheimer's disease pathology. Emerging literature indicates that mechanisms of aging and Alzheimer's disease are intricately linked and that these mechanisms can be modulated by both calorie restriction regimens and calorie restriction mimetics, the prime mediator of which is the SIRT1 protein, a human homologue of yeast silent information regulator (Sir)-2, and a member of NAD+-dependent histone deacetylases. Calorie restriction regimens and calorie restriction-mimetics trigger sirtuins in a wide variety of organisms, ranging from bacteria to mouse. In a mouse model of Huntington's disease, resveratrol-induced SIRT1 was found to protect neurons against ployQ toxicity and in Wallerian degeneration slow mice, resveratrol was found to protect the degeneration of neurons from axotomy, suggesting that resveratrol may possess therapeutic value to neuronal degeneration. This paper mainly focuses on the role of resveratrol in modulating AD pathomechanisms.

Aging↗
PubMed2005

Enzyme association with PPARgamma: evidence of a new role for 15-lipoxygenase type 2.

Fatty acids have historically important structural roles in contributing to epidermal barrier function and therefore cutaneous health. Their metabolism to bioactive compounds is often up-regulated in response to cutaneous toxins thus providing them with functional roles. Some metabolites of arachidonic acid, such as 15S-hydroxyeicosatetraenoic acid (HETE), also serve functional roles as direct ligands for peroxisome proliferator activated receptors (PPARs). 15S-HETE, produced by 15-lipoxygenase type 2 (15-LOX-2), is an endogenous ligand for PPARgamma. This report demonstrates epidermal keratinocyte expression of both 15-LOX-2 and PPARgamma and provides evidence for a relationship beyond that of ligand-producer and -user, namely in vivo association of the two proteins at the molecular level making the enzyme a candidate nuclear receptor coregulator. Such close physical approximation of the 15S-HETE-producing enzyme and PPARgamma could potentiate the receptor response to a short-lived ligand. 15-LOX-2 may exemplify a class of enzymatically active nuclear receptor coactivator proteins distinct from those previously described but sharing their ability to promote expression from nuclear receptor-regulated promoters.

Amino Acid Sequence↗
PubMed2005

Wanted: new multicomponent reactions for generating libraries of polycyclic natural products.

The amalgamation of two of combinatorial chemistry's most attractive concepts--natural product libraries and multicomponent reactions (MCRs)--should provide a powerful tactic for generating libraries of bioactive compounds. Yet, despite many recent advances in this area, only a few MCRs can deliver functionalized products whose structures closely resemble that of complex polycyclic natural products. A large proportion of recently developed MCRs are based on [4+2] or [3+2] cycloadditions, and isocyanide-based processes. Because of substrate limitations, however, they are not always ideally suitable for applications in diversity-oriented synthesis of natural product-like compounds. A promising area awaiting further development is the use of transition metal-catalyzed cascade reactions.

Biological Products↗
PubMed2005

Neurotoxic activity induced by a haemolytic substance in the extract of the marine sponge Geodia corticostylifera.

In our search for marine bioactive compounds we chose a Brazilian Coast sponge, Geodia corticostylifera (Demospongiae), whose extracts showed previously antibacterial and antifungal activities. In the present work we studied the following toxic properties of G. corticostylifera extract: neurotoxic (in mouse neuromuscular junction); mouse acute toxicity (IP) and haemolytic (against mouse and frog erythrocytes). Insertion of ionic channels in planar lipid bilayers in presence of a haemolytic purified fraction of the extract was observed. The toxic activities of G. corticostylifera crude extract are related to the formation of ionic pores in the cell membrane, which induce the release of haemoglobin from erythrocytes, and depolarization of nerve and muscle membranes. These last physiological effects cause the blockade of the diaphragm contractions, leading to death through respiratory arrest.

Animals↗
PubMed2005

Flash photolysis using a light emitting diode: an efficient, compact, and affordable solution.

Flash photolysis has become an essential technique for dynamic investigations of living cells and tissues. This approach offers several advantages for instantly changing the concentration of bioactive compounds outside and inside living cells with high spatial resolution. Light sources for photolysis need to deliver pulses of high intensity light in the near UV range (300-380 nm), to photoactivate a sufficient amount of molecules in a short time. UV lasers are often required as the light source, making flash photolysis a costly approach. Here we describe the use of a high power 365 nm light emitting diode (UV LED) coupled to an optical fiber to precisely deliver the light to the sample. The ability of the UV LED light source to photoactivate several caged compounds (CMNB-fluorescein, MNI-glutamate, NP-EGTA, DMNPE-ATP) as well as to evoke the associated cellular Ca(2+) responses is demonstrated in both neurons and astrocytes. This report shows that UV LEDs are an efficient light source for flash photolysis and represent an alternative to UV lasers for many applications. A compact, powerful, and low-cost system is described in detail.

Animals↗
PubMed2003

Binding structure of elastase inhibitor scyptolin A.

Natural bioactive compounds are of general interest to pharmaceutical research because they may be used as leads in drug development campaigns. Among them, scyptolin A and B from Scytonema hofmanni PCC 7110 are known to inhibit porcine pancreatic elastase, which in turn resembles the attractive drug target neutrophil elastase. The crystal structure of scyptolin A as bound to pancreatic elastase was solved at 2.8 A resolution. The inhibitor occupies the most prominent subsites S1 through S4 of the elastase and prevents a hydrolytic attack by covering the active center with its rigid ring structure. The observed binding structure may help to design potent elastase inhibitors.

Binding Sites↗
PubMed2004

Structure and biosynthesis of the jamaicamides, new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula.

A screening program for bioactive compounds from marine cyanobacteria led to the isolation of jamaicamides A-C. Jamaicamide A is a novel and highly functionalized lipopeptide containing an alkynyl bromide, vinyl chloride, beta-methoxy eneone system, and pyrrolinone ring. The jamaicamides show sodium channelblocking activity and fish toxicity. Precursor feeding to jamaicamide-producing cultures mapped out the series of acetate and amino acid residues and helped develop an effective cloning strategy for the biosynthetic gene cluster. The 58 kbp gene cluster is composed of 17 open reading frames that show an exact colinearity with their expected utilization. A novel cassette of genes appears to form a pendent carbon atom possessing the vinyl chloride functionality; at its core this contains an HMG-CoA synthase-like motif, giving insight into the mechanism by which this functional group is created.

Amides↗
PubMed2005

Dissection of melanogenesis with small molecules identifies prohibitin as a regulator.

Bioactive compounds can be used to selectively modulate gene function. We utilized a chemical genetic approach to dissect the mammalian pigmentation pathway and identify protein regulators. We screened a tagged library of 1170 small molecules in a cell-based assay and discovered a class of pigment-enhancing chemicals. From this class we characterized the small molecule melanogenin. Using melanogenin bound to an affinity matrix and amino acid sequencing, we identified the mitochondrial protein, prohibitin, as an intracellular binding target. Studies employing siRNA demonstrate that prohibitin is required for melanogenin to exert its propigmentary effects and reveal an unsuspected functional role for this protein in melanin induction. This represents a mechanism by which propigmentary signals are transduced and ultimately provides a potential target for the treatment of pigmentary disorders.

Amino Acid Sequence↗
PubMed2006

A robust small-molecule microarray platform for screening cell lysates.

Herein we report the expanded functional group compatibility of small-molecule microarrays to include immobilization of primary alcohols, secondary alcohols, phenols, carboxylic acids, hydroxamic acids, thiols, and amines on a single slide surface. Small-molecule "diversity microarrays" containing nearly 10,000 known bioactive small molecules, natural products, and small molecules originating from several diversity-oriented syntheses were produced by using an isocyanate-mediated covalent capture strategy. Selected printed bioactive compounds were detected with antibodies against compounds of interest. The new surface of the diversity microarrays is highly compatible with approaches involving cellular lysates. This feature has enabled a robust, optimized screening methodology using cellular lysates, allowing the detection of specific interactions with a broad range of binding affinity by using epitope-tagged or chimeric fluorescent proteins without prior purification. We believe that this expanded research capability has considerable promise in biology and medicine.

Cell Line↗
PubMed2006

Small-molecule screening identifies the selanazal drug ebselen as a potent inhibitor of DMT1-mediated iron uptake.

HEK293T cells overexpressing divalent metal transporter-1 (DMT1) were established to screen for small-molecule inhibitors of iron uptake. Using a fluorescence-based assay, we tested 2000 known bioactive compounds to find 3 small molecules that potently block ferrous iron uptake. One of the inhibitors, ebselen, is a seleno compound used in clinical trials as a protective agent against ischemic stroke. Ebselen inhibited Fe(II) uptake (IC(50) of approximately 0.22 microM), but did not influence Fe(III) transport or DMT1-mediated manganese uptake. An unrelated antioxidant, pyrrolidine dithiobarbamate (PDTC), also inhibited DMT1 activity (IC(50) of approximately 1.54 microM). Both ebselen and PDTC increased cellular levels of reduced glutathione. These observations indicate that Fe(II) transport by DMT1 can be modulated by cellular redox status and suggest that ebselen may act therapeutically to limit iron-catalyzed damage due to transport inhibition.

Antioxidants↗
PubMed2004

Preparative high-speed counter-current chromatography for purification of shikonin from the Chinese medicinal plant Lithospermum erythrorhizon.

The bioactive compound shikonin was successfully isolated and purified from the crude extract of the traditional Chinese medicinal plant Lithospermum erythrorhizon Sieb. et Zucc. by preparative high-speed counter-current chromatography (HSCCC). The preparative HSCCC was performed using a two-phase solvent system composed of n-hexane-ethylacetate-ethanol-water (16:14:14:5 (v/v)). A total amount of 19.6 mg of shikonin at 98.9% purity was obtained from 52 mg of the crude extract (containing 38.9% shikonin) with 96.9% recovery. The preparative isolation and purification of shikonin by HSCCC was completed in 200 min in a one-step separation.

Countercurrent Distribution↗
PubMed2004

Chromatographic analysis of alkylresorcinols and their metabolites.

Alkylresorcinols (AR) are phenolic lipids present in high amounts in the bran fraction of wheat and rye. AR are of scientific interest as bioactive compounds, as markers for the presence of wholegrain or bran fractions of wheat and rye in food products, and as possible biomarkers of intake for wholegrain wheat and rye. This review discusses their extraction from cereal grains, food and biological fluids, and the various chromatographic methods used in their analysis.

Chromatography, Gas↗
PubMed2004

Preparative isolation and purification of syringin and edgeworoside C from Edgeworthia chrysantha Lindl by high-speed counter-current chromatography.

The bioactive compound syringin along with edgeworoside C were separated from the n-butanol extract of the stems and barks of Edgeworthia chrysantha Lindl (E. papyrifera) by high-speed counter-current chromatography (HSCCC) while it was difficult to purify each compound by silica gel column chromatography. Syringin was isolated from this plant for the first time. The two-phase solvent system used was composed of ethyl acetate-ethanol-water at an optimized volume ratio of 15:1:15 (v/v/v). Preparative HSCCC yielded, from 110mg of the partially purified extract, 28mg of syringin and 45 mg edgeworoside C each at over 96% purity by high-performance liquid chromatography analysis. Their structures were identified by electron impact ionization MS, 1H NMR and 13C NMR.

Coumarins↗
PubMed2005

Preparative isolation and purification of germacrone and curdione from the essential oil of the rhizomes of Curcuma wenyujin by high-speed counter-current chromatography.

High-speed counter-current chromatography (HSCCC) was applied to isolate and purify bioactive compounds in the essential oil of the rhizomes of Curcuma wenyujin. Two sesquiterpenes germacrone and curdione were successfully isolated and purified using two-phase solvent system composed of petroleum ether-ethanol-diethyl ether-water (5/4/0.5/1, v/v) in tail to head elution mode. 62 mg of germacrone and 93 mg of curdione were obtained from 658 mg of the essential oil each at over 95% purity. Their structures were identified by 1H NMR and EI MS.

Chromatography, High Pressure Liquid↗
PubMed2005

Analysis of phenolic glycosides and saponins in Primula elatior and Primula veris (primula root) by liquid chromatography, evaporative light scattering detection and mass spectrometry.

This paper describes the first liquid chromatographic method suitable for the simultaneous determination of bioactive compounds, saponins and phenolic glycosides, present in Primula elatior and Primula veris, including the NMR data of primulaverin and primeverin. Optimum separations were obtained with a Synergi 4mum Fusion RP 80A column, using 0.025% TFA in water and 5% acetonitrile in methanol as mobile phase. Saponins were detected by evaporative light scattering detection (ELSD), whereas the phenolic glycosides were monitored by UV at 210 nm. The method was validated for repeatability (sigma(rel) or=97.1%) and sensitivity (LOD <or=22 ng (UV) and <or=38 ng (ELSD) on-column, respectively). LC-MS experiments in negative APCI mode allowed a final peak assignment. Both Primula species could easily be differentiated by their saponin pattern. The total saponin content was highest in P. veris roots (max. 14.9%), the aerial parts or P. elatior contained significantly less amounts; primeverin (0.64-1.42%) showed to be the most dominant phenolic glycoside.

Chromatography, Liquid↗