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 487 records · Page 27Linked to original sources
PubMed1978

New microbial secondary metabolites under preclinical development for cancer treatment.

Limitless numbers of various genetic structures have been formed in chromosomes and plasmids and numerous bioactive compounds are produced by microorganisms. Therefore, it may be said that compounds useful in treatment of cancer will be found more and more in microbial secondary metabolites and more effective antitumor antibiotics and their derivatives, or more effective products producing immune resistance to cancer, will be discovered. In these studies, as discussed in this paper, the most urgent problem is to establish a rational screening principle or system to select compounds worth clinical examination. This is particularly important in the analog area. Bleomycin is an analog of phleomycin chosen because of lower renal toxicity. It has become an antitumor agent of significant value. Macromycin is a new structure which has been found to bind with animal cells and inhibit growth. Neothramycin is a new benzodiazepine antibiotic which has lower toxicity than other structures studied in this class and is active against L1210, Yoshida sarcoma, and Sarcoma 180. Aclacinomycin A is an analog of adriamycin chosen for clinical study based on its low cardiac toxicity and high distribution in mouse lung and spleen. Coriolins are another new structural class. Diketocoriolin B has activity in L1210 leukemia and has been shown to inhibit Na-K-ATPase. Bestatin is a compound which inhibits aminopeptidase B and leucine aminopeptidase has been shown to increase delayed hypersensitivity. Bestatin also increases the effects of other antitumor agents such as adriamycin, and bleomycin.

Animals↗
PubMed2005

Screening for new metabolites from marine microorganisms.

This article gives an overview of current analysis techniques for the screening and the activity analysis of metabolites from marine (micro)organisms. The sequencing of marine genomes and the techniques of functional genomics (including transcriptome, proteome, and metabolome analyses) open up new possibilities for the screening of new metabolites of biotechnological interest. Although the sequencing of microbial marine genomes has been somewhat limited to date, selected genome sequences of marine bacteria and algae have already been published. This report summarizes the application of the techniques of functional genomics, such as transcriptome analysis in combination with high-resolution two-dimensional polyacrylamide gelelectrophoresis and mass spectrometry, for the screening for bioactive compounds of marine microorganisms. Furthermore, the target analysis of antimicrobial compounds by proteome or transcriptome analysis of bacterial model systems is described. Recent high-throughput screening techniques are explained. Finally, new approaches for the screening of metabolites from marine microorganisms are discussed.

Bacteria↗
PubMed1994

Distribution patterns of the paraneuronal endocrine cells in the skin, gills and the airways of fishes as determined by immunohistochemical and histological methods.

The neuro-endocrine cells of fish skin and respiratory surfaces, and their bioactive secretion as far as is known, are reviewed, and compared with similar elements in tetrapods, particularly amphibians. In the skin of teleost fish, immunohistochemistry has shown that Merkel cells react for serotonin, neuron-specific enolase and enkephalins. The pharmacology is not established in dipnoans or lampreys. In some teleosts, neuromasts react for substance P and leu-enkephalins; substance P is also reported from some ampullary organs (electroreceptors). Taste buds of teleosts may react for enkephalin and substance P. Basal cells of taste buds react for serotonin and neuron-specific enolase. Some unicellular skin glands of teleosts express bioactive compounds, including serotonin and some peptides; this ectopic expression is paralleled in amphibian skin glands. The dipnoan Protopterus has innervated pulmonary neuro-endocrine cells in the pneumatic duct region with dense-cored vesicles. In Polypterus and Amia the lungs have serotonin-positive neuro-endocrine cells that are apparently not innervated. In fish gills, a closed type of neuro-endocrine cell reacts for serotonin, an open type for enkephalins and some calcium-binding proteins (calbindin, calmodulin and S-100 protein). The functions of neuro-endocrine cells in fishes await investigation, but it is assumed they are regulatory.

Animals↗
PubMedDate not supplied

Significance of myocardial eicosanoid production.

The precise role of eicosanoids in the development of myocardial injury during ischemia and reperfusion is still a matter of debate. Enhanced local production of these bioactive compounds appears to be a common response to tissue injury. Most likely, the cardiac tissue has the capacity to generate prostaglandins, thromboxanes as well as leukotrienes. Prostacyclin (PGI2) is the major eicosanoid produced by the jeopardized myocardium. In addition, at sites of tissue injury activation of platelets and infiltrating leukocytes results in the formation of considerable amounts of thromboxanes and leukotrienes. The production of eicosanoids requires prior release of arachidonic acid (AA) from phospholipids. Both ischemia and reperfusion are associated with a rise in the tissue level of AA. The absence of a proportional relationship between the tissue level of AA and the amounts of PGI2 produced suggests that the sites of AA accumulation and PGI2 formation are different. It is conceivable that AA accumulation is mainly confined to myocytes, whereas the capacity to synthesize PGI2 mainly resides in vascular cells. Both beneficial and detrimental effects of eicosanoids on cardiac tissue have been described. Prostaglandins act as vasodilators. Besides, some of the prostaglandins, especially PGI2, are thought to possess cyto-protective properties. Thromboxanes and leukotrienes may impede blood supply by increasing smooth muscle tone. Besides, leukotrienes augment vascular permeability. Experimental studies, designed to evaluate the effect of pharmacological agents, like PGI2-analogues and lipoxygenase and cyclo-oxygenase inhibitors, indicate that eicosanoids influence the outcome of myocardial injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Subcellular distribution of coronary dilatatory protein-hormonal complexes in rat hypothalamus.

We previously reported the presence of a group of coronary dilatatory protein-carriers of the cardioactive neurohormones and precursors of bioactive compounds in the hypothalamus of some animals. Investigation of the subcellular distribution of those proteins revealed their localization in neurosecretory granules and in synaptosomes of the hypothalamus. In further investigation of the regional distribution of coronary-active proteins in different parts of the brain they were found in synaptosomes of the cerebral cortex too. The main location of coronary-active proteins in synaptosomes indicates their participation in synaptic functions.

Animals↗
PubMed1995

Vitamin D sites and mechanisms of action: a histochemical perspective. Reflections on the utility of autoradiography and cytopharmacology for drug targeting.

Knowledge about sites and mechanisms of action of vitamin D and its analogs has been greatly advanced by histochemical approaches. High resolution and high sensitivity, combined with the integrative potential of relatively intact histochemical tissue preparations, contributed information that is difficult or impossible to obtain otherwise. In in vivo distribution studies with conventional biochemical assays, target cell populations associated with non-target tissues frequently remain unrecognized without the resolution achieved by cellular autoradiography. Autoradiography, alone or combined with immunohistochemistry when applied to in vivo drug targeting and target characterization, has provided information on cellular-subcellular receptor distribution in over 50 tissues. These discoveries, importantly, contribute to a new understanding of the biological role of vitamin D and challenge the concept of "the calcium homeostatic steroid hormone" as being too narrow. While some of the outstanding effects of vitamin D deficiency and toxicity relate to calcium homeostasis, the vast majority of the target tissues appear not to be primarily related to calcium metabolism, but rather to the activation and regulation of exo- and endocrine secretory and somatotrophic processes such as cell differentiation and proliferation. Also, several highly calcium-dependent tissues such as striated and smooth muscles are not genomic targets for vitamin D. The reviewed data on the diverse and extensive presence of target tissues forecast a high therapeutic potential for vitamin D and especially its low-calcemic analogs, far beyond that which is presently utilized. The evidence provided for vitamin D also testifies to the utility and need to include in vivo cytopharmacology in any target evaluation of bioactive compounds to further the understanding of their mechanisms of action, and to identify preferential targets and their differential therapeutic and toxic potentials.

Animals↗
PubMed1991

The role of medicinal chemistry in drug research.

Classical medicinal chemistry, that is molecular modifications of existing bioactive compounds, leading to me-too drugs with value added and often to me-too drugs which will never reach the market or to drugs in another pharmacological field than that originally intended, will be with us for a long time to come. The ultimate goal, however, is of course rational or at least semi-rational drug design. In some instances this goal seems to have already been reached as in the case of angiotensin-converting enzyme inhibitors and H2 antagonists. In the (near) future results from the steady progress in molecular biology in combination with computer-assisted drug modelling--possibly coupled with artificial intelligence techniques--will help the medicinal chemist in his efforts to attain this goal.

Animals↗
PubMed1998

Preliminary study on the suitability of a pharmacological bio-assay based on cardiac myocytes cultured over microfabricated microelectrode arrays.

There are a range of techniques that can be used to assay bioactive compound. One potentially promising technique is a system consisting of microfabricated extracellular recording devices over which electrogenic cells can be grown. To date, research in this area has concentrated on the use of neurons as an electrogenic cell type. However, these cells have limitations. Only small extracellular potentials have been recorded from mammalian neurons cultured over microfabricated electrode arrays. Although such potentials may be of use in assays examining the effects of bio-active compound analogues on firing frequency, they are of little use for more detailed pharmacological studies involving analyses of signal shape. What is required is a system from which much larger extracellular potentials can be recorded. This preliminary study reports on a system based on cardiac myocytes cultured over microfabricated metal microelectrode arrays, from which potentials with a mean amplitude of 16.9 microV can be reliably recorded, which can be reversibly blocked with mumoll-1 concentrations of the sodium ion channel blocker lidocaine. Less common potentials with amplitudes of up to 3.5 mV were also recorded. It is demonstrated that cardiac myocytes cultured over microfabricated micro-electrode arrays can be used in assays of cardioactive compound analogues.

Animals↗
PubMed1988

Microtiter micromass cultures of limb-bud mesenchymal cells.

A method is described for growing high-density micromass cultures of chick and mouse limb mesenchyme cells in 96-well microtiter plates (microT microM cultures). Rapid quantitative estimates of chondrogenic expression were obtained by automated spectrophotometric analysis of Alcian-blue-stained cartilage matrix extracts performed in the wells in which the cells had been grown. Quantitative estimates of myogenic expression were obtained similarly using anti-sarcomere myosin monoclonal antibody and modified ELISA techniques. This microT microM-ELISA method may be adapted for use with other antigens for which specific antibodies are available. These methods were used to compare cartilage and muscle differentiation in 1 to 4 d microT microM cultures grown in serum-containing (SCM) and defined (DM) media. The DM contains minimal additives (insulin, hydrocortisone, and in some cases, ascorbate or transferrin) and supports both chondrogenesis and myogenesis. The colorimetric analyses agree well with the morphologic appraisal of chondrogenesis and myogenesis. Similar numbers of cartilage nodules formed in all cultures, but in DM the nodules failed to enlarge; explaining the reduced matrix synthesis in DM as compared with SCM, and suggesting that nodule enlargement is a discrete, serum-dependent step. Studies of selected additives to DM show that transferrin enhances myogenesis, ascorbic acid enhances chondrogenesis, and retinoic acid inhibits chondrogenesis. Together, the microT microM system, in situ colorimetric assays of chondrogenesis and myogenesis, and DM will allow rapid prescreening of teratogens and screening of various bioactive compounds (e.g., hormones, growth factors, vitamins, adhesion factors) for effects on limb mesenchymal cell differentiation.

Animals↗
PubMed1998

Biological effects of macrotetrolide antibiotics and nonactic acids.

Published results as well as patent applications on biological effects of macrotetrolides and nonactic acids are reviewed. Their antimicrobial, antiprotozoan (coccidiostatic), antiparasitic (anthelminthic), insecticidal and acaricidal (miticidal) effects and also newly described immunosuppressive and plant growth stimulating activities are described. Both theoretical papers and practical applications including the effects of macrotetrolides on the environment are included; a particular target organism and precise dosage (e.g. LD50) are reported, in agreement with the original papers. It appears that macrotetrolides and their homologs are very prospective bioactive compounds that find application in agriculture, forestry, human and veterinary medicine while their negative effects on the environment are restricted to a minimum (biological quality of soil and water etc.).

Animals↗
PubMed2006

Chemical constituents of the root of Dystaenia takeshimana and their anti-inflammatory activity.

In our ongoing search for bioactive compounds originating from the endemic species in Korea, we found that the hexane and EtOAc fractions of the MeOH extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin D2 (PGD2) and leukotriene C4 (LTC4) in mouse bone marrow-derived mast cells. By activity-guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3), scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with beta-sitosterol (1), were isolated from the hexane fraction, and two phenethyl alcohol derivatives, viz. 2-methoxy-2-(4'-hydroxyphenyl)ethanol (7) and 2-hydroxy-2-(4'-hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (10), and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc fraction using silica gel column chromatography. In addition, D-mannitol (13) was isolated from the BuOH fraction by recrystallization. Two of the coumarins, scopoletin (4) and (+)-marmesin (6), the two phenethyl alcohol derivatives (7, 8) and the three flavonoids (9-11) were isolated for the first time from this plant. Among the compounds isolated from this plant, the five coumarins as well as the three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results suggest that the anti-inflammatory activity of D. takeshimana might in part occur via the inhibition of the generation of eicosanoids.

Animals↗
PubMed2006

The role of the hydrophobic group on ring A of chalcones in the inhibition of interleukin-5.

Novel chalcones were found as potent inhibitors of interleukin-5 (11-5). 1-(6-Benzyloxy-2-hydroxyphenyl)-3-(4-hydroxyphenyl)propenone (2a, 78.8% inhibition at 50 microM, IC50 = 25.3 microM) was initially identified as a potent inhibitor of IL-5. This activity is comparable to that of budesonide or sophoricoside (1a). The benzyloxy group appears to be critical for the enhancement of the IL-5 inhibitory activity. To identify the role of this hydrophobic moiety, cyclohexyloxy (2d), cyclohexylmethoxy (2c), cyclohexylethoxy (2e), cyclohexylpropoxy (2f), 2-methylpropoxy (2g), 3-methylbutoxy (2h), 4-methylpentoxy (2i), and 2-ethylbutoxy (2j) analogs were prepared and tested for their effects on IL-5 bioactivity. Compounds 2c (IC50 = 12.6 microM), 2d (IC50 = 12.2 microM), and 2i (IC50 = 12.3 microM) exhibited the most potent activity. Considering the cLog P values of 2, the alkoxy group contributes to the cell permeability of 2 for the enhancement of activity, rather than playing a role in ligand motif binding to the receptor. The optimum alkoxy group in ring A of 2 should be one that provides the cLog P of 2 in the range of 4.22 to 4.67.

Cell Line↗
PubMed2006

In vitro anti-cariogenic activity of dichloromethane fraction from Rheum undulatum L. root.

This study aimed to evaluate in vitro effects of Rheum undulatum L. root on the development of dental caries, especially its effects on viability, dental plaque formation, and glycolytic acid production of Streptococcus mutans and Streptococcus sobrinus. Methanol extract of Rheum undulatum L. root and its fractions were prepared and tested. Among the test extract and fractions, dichloromethane fraction (DF) showed the most active antibacterial activity (inhibition zone: 13-17 mm) against S. mutans and S. sobrinus in a disc diffusion method. Minimal inhibitory concentrations (MICs) of DF against these bacteria ranged from 0.25 to 0.5 mg/mL. Furthermore, DF significantly inhibited the caries-inducing factors of these bacteria. At sub-MIC levels, DF inhibited in vitro dental plaque formation by S. mutans and S. sobrinus (IC50= 0.079 and 0.142 mg/mL, respectively), which was caused, in part, by the inhibitory effect on the activity of glucosyltransferases. A significant reduction of glycolytic acid production was found at the concentration as low as 0.032 mg/mL for S. mutans and 0.063 mg/mL for S. sobrinus. The possible bioactive compounds that are inducing in vitro anti-cariogenic activity of DF are unknown. Based on the preliminary phytochemical analysis, the activity of DF may be related to the presence of anthraquinones, cardiac glycosides, coumarines, sterols/terpenes, and phenolics. These results indicate that DF is probably useful for the control of dental plaque formation and subsequent dental caries development.

Anti-Bacterial Agents↗
PubMed2004

Isolation of flavonol rhamnosides from Loranthus tanakae and cytotoxic effect of them on human tumor cell lines.

Loranthus tanakae Fr. et Sav. (Loranthaceae) is a species of mistletoe, a semiparasitic plant growing on the branches of Quercus and Betula species as host trees. In our ongoing search for bioactive compounds from endemic species in Korea, we have investigated to isolate the chemical constituents responsible for the antitumor effect of the MeOH extract of L. tanakae. The ethylacetate soluble part of the MeOH extract demonstrated a marginal inhibition on the proliferation of the tumor cell lines such as A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system), and HCT-15 (colon) in vitro. Thus, the activity-guided isolation procedure upon the ethylacetate soluble part of the extract has been carried out and finally four flavonoid rhamnopyranosides (1-4) were isolated as active principle. The structures of 1-4 were elucidated by the physicochemical and spectral data as rhamnetin 3-O-alpha-L-rhamnoside (1), quercetin 3-O-alpha-L-rhamnoside (2), rhamnocitrin 3-O-alpha-L-rhamnoside (3), and kaempferol 3-O-alpha-L-rhamnoside (4).

Animals↗
PubMed2005

Anti-allergic effects of natural tetranortriterpenoids isolated from Carapa guianensis Aublet on allergen-induced vascular permeability and hyperalgesia.

OBJECTIVE: We investigated the anti-allergic and analgesic properties of an oil and a derived fraction of tetranortriterpenoids (TNTP) obtained from the seeds of Carapa guianensis Aublet. MATERIALS AND METHODS: Pleurisy, paw and ear edema were induced in Swiss and C57/Bl10 mice mice, whereas thermal hyperalgesia was assessed in Wistar rats (n = 6-10 per group). Values of p < 0.05 were regarded as significant. RESULTS: C. guianensis oil (100 to 400 mg/kg, p.o.) and TNTP (12.5 to 100 mg/kg, p.o.) inhibited pleural exudation, paw and ear edema induced by ovalbumin (OVA) in sensitized mice. TNTP (12.5 to 100 mg/kg, p.o.) also inhibited paw edema induced by histamine, PAF and bradykinin. TNTP (100 mg/kg, p.o.) inhibited prostaglandin E(2) generation in the pleural cavity in response to antigenic challenge. Moreover, C. guianensis oil (100 to 400 mg/kg) and TNTP (12.5 to 100 mg/kg) decreased OVA- and histamine-induced hyperalgesia. CONCLUSION: Taken together, these findings demonstrate the anti-edematogenic and analgesic effects of C. guianensis oil, and points out TNTP as the responsible bioactive compounds.

Allergens↗
PubMed1998

Dynamic insulin secretion from perifused rat pancreatic islets.

Insulin secretion from isolated pancreatic islets of 8- to 12-day-old rats was investigated in a dynamic in vitro (perifusion) system. The aims of the study were (i) to describe a carefully controlled in vitro method to study the mechanism of insulin secretion and to analyse the effects and dynamic interactions of bioactive compounds on isolated rat pancreatic islets, (ii) to validate the method by comparing fundamental data on the functions of the islets obtained with this method to those collected with other techniques; and (iii) to find novel features of the control of insulin secretion. The method was carefully designed to maintain the functional capacity of the explanted cells. A functional standardization system was elaborated consisting of (i) analysis of the changes in the basal hormone secretion of the cells; (ii) evaluating responses to a standard, specific stimuli (50 mM glucose for 3 min); (iii) determining the alteration of the momentary size of the hormone pool with responses to KCl; and (iv) direct determination of the total intracellular hormone content from the extract of the column. The technique provides accurate quantitative data on the dynamic responses to biologically active compounds that act directly on the pancreatic islets. The islets maintained their full responsiveness for up to 7 days, and responses as close as in 1-min intervals could be distinguished. A linear dose-response relationship was found on the glucose-induced insulin release in case of 3-min stimulation with 4 and 500 mM of glucose (lin-log graph). Utilizing this method, we showed that no desensitization to glucose-induced insulin release can be observed if the responsiveness of the cells is properly maintained and the parameters of the stimulation are carefully designed. Exposure of the explanted islets to 10 microM acetylcholine or 30 mM arginine (Arg) induced a transitory elevation of insulin release similar in shape to that experienced after glucose stimulation. Norepinephrine (NE), dopamine (DA) and somatostatin (SS) did not induce any detectable alteration on the basal insulin secretion of the islets. However, 100 nM SS given together with 50 mM glucose, 30 mM Arg or 10 microM acetylcholine significantly reduced the insulin-releasing effect of these substances (by 75.5, 71.5 and 72.5%, respectively). At the same time, SS did not alter the insulin response of the islets to 100 mM elevation of K+ concentration. SS also inhibited glucose-induced insulin release in a dose-dependent way (ED50 = 22 nM). A similar dose-dependent inhibitory effect on glucose-induced insulin release was found with NE (ED50 = 89 nM) and DA (ED50 = 2.2 microM). gamma-Aminobutyric acid (GABA) did not influence insulin release under similar circumstances.

Acetylcholine↗
PubMed2005

LC-DAD-APCI-MS-based screening and analysis of the absorption and metabolite components in plasma from a rabbit administered an oral solution of danggui.

A valid chromatographic fingerprint method using liquid chromatography-diode array detection-atmospheric pressure chemical ionization mass spectrometry in negative mode (LC-DAD-APCI-MS) is proposed for studying the absorption and metabolites of a traditional Chinese medicine (TCM) Angelica sinensis (danggui) in rabbit plasma, after the rabbit is administered with danggui oral solution (DOS). More than thirty-two common components were detected in both DOS and rabbit plasma, which shows that the components in the DOS were absorbed into the body of the rabbit. Of these, senkyunolide I, senkyunolide H, Z-6,7-epoxyligustilide, 3-butylidene-7-hydroxyphthalide, Z-ligustilide, Z-butylidenephthalide, Diels-Alder dimers of ligustilide, linolenic acid, linoleic acid and falcarindiol were tentatively identified from their MS, UV spectra and retention behavior by comparing the results with the published literature. At least ten components were found in rabbit plasma but not in DOS, indicating that these components must be metabolites of some of the components in the original extract. The results prove that the proposed method can be used to rapidly analyze multiple constituents in TCMs, and to screen for bioactive compounds by comparing and contrasting the chromatographic fingerprints of DOS and plasma samples.

4-Butyrolactone↗
PubMed2006

Isolating the whole complex of target proteins of FK506 using affinity resins from novel solid phases.

The development of novel solid phases enabled us to create affinity resins that could be used to isolate the whole complex of target proteins responsible for the immunosuppressive effects of FK506 from rat brain lysate, whereas the affinity resins from commercially available matrices could not achieve this isolation. The results illustrate the enhanced effectiveness of the affinity resin made from this novel material at identifying the target protein of the bioactive compound compared to resins made from the well-known materials Affigel or Toyopearl. This effectiveness arises because the novel material is hydrophilic enough to reduce nonspecific binding proteins and because it has a higher density of ligands that capture the nonubiquitous target protein.

Animals↗