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At least 1,225 records · Page 68Linked to original sources
PubMed1995

Bio-active compounds from Psychotria camponutans.

A new benzoquinone (1-hydroxybenzoisochromanquinone) and benz [g]isoquinoline-5, 10-dione have been isolated from the woody parts of Psychotria camponutans, as a result of bioactivity-guided fractionation. The compounds were characterized by UV, IR, EI-mass, 1H-, and 13C-NMR, and HETCOR NMR spectroscopy. Both compounds, together with acetylbenzoisochromanquinone, showed in vitro strong activity against brine shrimp, KB cells, and chloroquine-resistant P. falciparum.

Animals↗
PubMed2006

Structure-activity relationship study of 9-aminoacridine compounds in scrapie-infected neuroblastoma cells.

A focused library of variously substituted 9-aminoacridine compounds was screened for bioactivity against accumulation of the infectious prion protein isoform, denoted PrP(Sc), in a cell model of prion replication. The efficacy of compounds against PrP(Sc) accumulation was influenced by both substituents of the distal tertiary amine and acridine heterocycle, while cellular cytotoxicity was encoded in the acridine heterocycle substituents.

Aminacrine↗
PubMed2006

[Synthesis and bioactivity of 2-arylimino-4-thiazolidones].

AIM: To synthesize a series of 2-arylimino-4-thiazolidone derivatives and 2-imidazolino [2,3-b]-4-thiazolidone in order to get some novel potent compounds with nitric oxide synthases (NOS) inhibitory activity. METHODS: The target compounds were prepared by reaction of N-chloroacetyl-1,2,3,4-tetrahydroisoquinoline or N-chloroacetylphthalimide with substituted thioureas, their NOS inhibitory activity were measured. RESULTS AND CONCLUSION: The 15 new compounds were synthesized and most of the reaction yields were over 65%. The structures of new compounds were identified by IR, 1H NMR, MS and elemental analyses. Bioassay indicated that, most of 15 new compounds synthesized had confirmed bioactivities inhibition against NOS.

Molecular Structure↗
PubMed1989

Structural requirements of lipid A for endotoxicity and other biological activities.

For the past ten years, several groups were engaged in synthetic studies of lipid A, namely the lipid portion of bacterial lipopolysaccharides (LPS) that has been assumed to be the bioactive center of LPS, but has not been unanimously approved. Among them, Shiba, Kusumoto, and colleagues, Osaka, Japan have synthesized most energetically and successfully a variety of counterparts of lipid As, biosynthetic lipid A precursors, and their analogs. The endotoxic and related bioactivities of these synthetic compounds were studied by Japanese and German groups, including ours. In 1985, one of the compounds, having an acylation and phosphorylation pattern in beta(1-6)-D-glucosamine disaccharide which was proposed for Escherichia coli F515 lipid A was found to be exhibit full endotoxic and related bioactivities identical to those of the bacterial product. The study was extended by synthesis and examination of bioactivities of variously acylated D-glucosamine di- and monosaccharide phosphates, which correspond to structural components of lipid As, and their analogs or derivatives. Thus, structural requirements have been fairly well elucidated. In this article, first we will review the progress of synthetic and biological studies, with particular emphasis on chemical structure--bioactivities relationships of lipid As, and then we will discuss possible usefulness of some less or nontoxic lipid A-related synthetic compounds in clinical and preventive medicine.

Adjuvants, Immunologic↗
PubMed1995

Quantitative binding site model generation: compass applied to multiple chemotypes targeting the 5-HT1A receptor.

We present enhancements to the Compass algorithm that automatically deduce interchemotype relationships and generate predictive quantitative models of receptor binding based solely on structure-activity data. We applied the technique to a series of compounds assayed for 5-HT1A binding. A model was constructed from 20 compounds of two chemotypes and used to predict the affinities and bioactive conformation of 35 new compounds, most of which had new underlying scaffolds and/or functional groups. The model's mean error of prediction was 0.5 log units (essentially the assay resolution), even on quite divergent series. The predictions are supported by an interpretable hypothesis for the binding determinants of the receptor and the geometric relationships of the chemotypes.

Algorithms↗
PubMed2002

Prevention by polyhydroxysteroids and saponins of Asterina pectinifera of the desquamation of stratum corneum cells.

Two polyhydroxysteroids and three steroidal saponins (pectiniosides A, B and C) were isolated as bioactive substances from Asterina pectinifera. These compounds inhibited the release of guinea-pig skin stratum corneum cells by 48-67% (control, 0%) at 2 mg/ml. It is suggested that the bioactivity of these compounds is connected with the remedial and preventive effects of an aqueous extract of A. pectinifera on rough human skin.

Animals↗
PubMed2002

Vinyl sulfide cyclized analogues of angiotensin II with high affinity and full agonist activity at the AT(1) receptor.

Vinyl sulfide cyclized analogues of the octapeptide angiotensin II that are structurally related to the cyclic disulfide agonist c[Hcy(3,5)]Ang II have been prepared. The synthesis relies on the reaction of the mercapto group of a cysteine residue in position 3 with the formyl group of allysine incorporated in position 5 of angiotensin II. A mixture of the cis and the trans isomers was formed, and these were separated and isolated by RP-HPLC. Thus, the three-atom CH(2)[bond]S[bond]S element of the AT(1) receptor agonist c[Hcy(3,5)]Ang II has been displaced by a bioisosteric three-atom S[bond]CH[double bond]CH element. A comparative conformational analysis of the 13-membered ring systems of c[Hcy(3,5)]Ang II and the 13-membered cyclic vinyl sulfides with cis and trans configuration, respectively, suggested that all three systems adopted very similar low-energy conformations. This similarity was also reflected in the bioactivity. Both of the compounds that contained the ring systems encompassing the cis or trans vinyl sulfide elements between positions 3 and 5 exhibited K(i) values less than 2 nM and exerted full agonism at the AT(1) receptor. In contrast, vinyl sulfide cyclization involving the amino acid residues 5 and 7 rendered inactive compounds. The cyclic vinyl sulfides that have agonist activity were both shown to possess low-energy conformers compatible with the previously proposed 3D model for the bioactive conformation of Ang II.

Angiotensin II↗
PubMed1976

Synthesis and antihypertensive activity of some imidazoindole derivatives.

The synthesis of pyridino[1,2-a]imidazo[5,4-b]indole (1) and thiazolo[3,2-a-a]imidazo[5,4-b-a]indole (2) has been achieved by phosphite reduction of 3-nitroso-6-phenylimidazo[1,2-a]pyridine and 5-nitroso-6-phenylimidazo[2,1-bb]thiazole. Compound 1 has shown strong antihypertensive activity in spontaneously hypertensive rats while compound 2 showed similar bioactivity both in spontaneously hypertensive rats and in normotensive dogs. A tricyclic amino derivative, 3-amino-2-phenylimidazo[1,2-a]pyridine, which has structural resemblance to compound 1, showed no hypotensive activity.

Animals↗
PubMed2004

Therapeutic applications of lipid-coated microbubbles.

Lipid-coated microbubbles represent a new class of agents with both diagnostic and therapeutic applications. Microbubbles have low density. Stabilization of microbubbles by lipid coatings creates low-density particles with unusual properties for diagnostic imaging and drug delivery. Perfluorocarbon (PFC) gases entrapped within lipid coatings make microbubbles that are sufficiently stable for circulation in the vasculature as blood pool agents. Microbubbles can be cavitated with ultrasound energy for site-specific local delivery of bioactive materials and for treatment of vascular thrombosis. The blood-brain barrier (BBB) can be reversibly opened without damaging the neurons using ultrasound applied across the intact skull to cavitate microbubbles within the cerebral microvasculature for delivery of both low and high molecular weight therapeutic compounds to the brain. The first lipid-coated PFC microbubble product is currently marketed for diagnostic ultrasound imaging. Clinical trials are currently in process for treatment of vascular thrombosis with ultrasound and lipid-coated PFC microbubbles (SonoLysis Therapy). Targeted microbubbles and acoustically active PFC nanoemulsions with specific ligands can be developed for detecting disease at the molecular level and targeted drug and gene delivery. Bioactive compounds can be incorporated into these carriers for site-specific delivery. Our aim is to cover the therapeutic applications of lipid-coated microbubbles and PFC emulsions in this review.

Blood-Brain Barrier↗
PubMed2001

Bioactive constituents of the roots of Licania intrapetiolaris.

Fractionation of a methanol extract of the roots of Licania intrapetiolaris, as directed by activity against the KB assay, has led to the isolation of two novel clerodane diterpenoids, intrapetacins A (1) and B (2), and the known triterpenoid cucurbitacin B (3). The structures of 1 and 2 were deduced from one- and two-dimensional NMR experiments, including relative stereochemical assignments based on NOESY correlations and COSY coupling constants. Compound 3 was the most potent against the KB assay, but both 1 and 2 displayed moderate cytotoxicity. When evaluated against an antifungal assay using Aspergillus niger, 2 caused a significant zone of inhibition of fungal growth, while 1 was completely inactive. To the best of our knowledge, this is the first report of the isolation of bioactive compounds from the genus Licania.

Aspergillus niger↗
PubMed2001

Synthesis and application of caged peptides and proteins.

Caged compounds have covalently attached groups that are rapidly cleaved upon exposure to UV light. Attachment of photolabile groups makes the molecule inert until photolysis releases it in its bioactive form. When caged compounds are applied to the experimental system in advance, the concentration jump of biologically active substances can be brought about immediately in a limited area upon irradiation with pulsed and focused UV light. Therefore, caged compounds of low molecular weight, which are commercially available, have been used effectively to study the mechanisms of temporal biological phenomena, such as muscle contraction, intracellular signaling, and neurotransmission. Because many proteins and peptides play important roles in these phenomena, their caged derivatives should serve as powerful tools to clarify complex biological systems. To prepare caged proteins and peptides, several groups have improved upon a chemical modification method, as well as developed two new methods: (1) nonsense codon suppression and (2) solid-phase peptide synthesis. In this review, we summarize recent advances made in the design, preparation, and application of caged peptides and proteins.

Biological Availability↗
PubMed2006

Determination and mapping of activity-specific descriptor value ranges for the identification of active compounds.

MAD (Mapping to Activity class-specific Descriptor value ranges) is a novel molecular similarity method that relies on the identification of activity-specific descriptors. Applying a categorical descriptor scoring function, value ranges of molecular descriptors in screening databases are compared with those in classes of active compounds and descriptors displaying significant deviations are selected. In order to identify new actives, database molecules are mapped to class-specific value ranges and ranked using a similarity function. As a mapping algorithm, MAD is distinct from many other molecular similarity and virtual screening methods. In systematic virtual screening trials, for small selection sets of only 30 database compounds, average hit and recovery rates over six activity classes ranged from about 10% to 25% and about 25% to 75%, respectively. Moreover, when mining a database of bioactive molecules many similar compounds were selected (with hit rates between about 15% and 79%). Our findings suggest that it is possible to generate compound class-directed descriptor reference spaces for molecular similarity analysis.

Algorithms↗
PubMed2004

[Synthesis and antitumor activities of 10-hydroxy camptothecin derivatives].

AIM: To find new anticancer drug based on the structure of 10-hydroxy camptothecin. METHODS: Seven camptothecin derivatives (3 -9) were synthesized and the antitumor activities of these derivatives were evaluated. RESULTS: Structures of seven new compounds were determined by 1HNMR, IR, MS. Seven compounds showed inhibitory effects on Hela, BEL-7402, 7901 cell lines in vitro. Especially, compound 4 showed high bioactivities to all of the tumor cells in vitro, its anticancer activity against human cervical carcinoma Hela was much higher than that of 10-hydroxy camptothecin. CONCLUSION: Some compounds are worth further studying.

Antineoplastic Agents↗
PubMed1992

Non-enzymatic activation of procarbazine to active cytotoxic species.

The cellular cytotoxicity of procarbazine is thought to result from bioactivation of the parent compound through reactive intermediates to an ultimate alkylating species. Procarbazine is converted initially to azoprocarbazine, which is then N-oxidized through a cytochrome P-450-mediated process to a mixture of the positional isomers, benzylazoxyprocarbazine and methylazoxyprocarbazine. In order to define the bioactivation events that lead to the cytotoxic species, the in vitro cytotoxicities of the purified azoxy isomers as well as of the parent compound, procarbazine, were evaluated with the human leukemia cell line, CCRF-CEM. The methylazoxy isomer was found to be the most active species. Procarbazine inhibited the growth of CCRF-CEM cells but at a concentration much higher than that required for the methylazoxy isomer. Since procarbazine must be metabolized to form the cytotoxic species, we sought to determine if the active metabolite, methylazoxyprocarbazine, was being formed in the incubations. Solutions of procarbazine incubated with and without cells at 37 degrees C were analyzed by combined liquid chromatography-mass spectrometry with a thermospray interface. The azoxy metabolites of procarbazine appeared rapidly in cellular incubations and in the aqueous solutions without cells. More of the methylazoxy isomer was formed initially, but by 72 hr the benzylazoxy isomer was the predominant species. Thus, in these studies it appears that procarbazine was benzylazoxy isomer was the predominant species. Thus, in these studies it appears that procarbazine was non-enzymatically oxidized to the two azoxyprocarbazine isomers and that the methylazoxy compound was the most cytotoxic to CCRF-CEM cells.

Biotransformation↗
PubMed2004

Separation methods of quinonoid constituents of plants used in Oriental traditional medicines.

Analysis of molecular constituents of traditional Oriental medicines has acquired a fresh perspective in view of a surge in interest in the consumption of herbal prescriptions all over the world. Several of them contain quinonoid compounds, and the long-standing therapeutic applications of these herbs have been vindicated, to some extent, through recent studies on the significant pharmacological properties of these compounds. In fact, the bioactive quinonoids and their analogues often serve as the 'marker' constituents of the respective plants of major commercial importance. Hence, shikonin, plumbagin, diospyrin, emodin analogues, sennosides, hypericin, tanshinone and related compounds have been discussed in this review which focuses on their extraction, separation and analysis from plant sources, cell cultures and biological fluids. As for the analysis of quinonoids, high-performance liquid chromatography connected with various detectors (ultraviolet, photodiode array, fluorescence, mass, nuclear magnetic resonance) has been the most useful technology succeeding the conventional methods such as thin layer and column chromatography. In some cases, high-performance thin layer chromatography and capillary electrophoresis are also used for this purpose.

Medicine, Chinese Traditional↗
PubMed1999

Conformational considerations in the design of dual antagonists of platelet-activating factor (PAF) and histamine.

Following the discovery of the first dual antagonist of platelet-activating factor (PAF) and histamine, 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin- 11-ylidene)piperidine, Sch 37370, 1, a related series of structures, exemplified by (+/-)-1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b] pyridin-11-yl)piperazine, Sch 40338, 2, were prepared. Interestingly, the compounds exhibited a parallel structure antiallergy activity relationship, suggesting that the two series may adopt a common conformation at the PAF receptor. Conformational analysis led to a proposal for this bioactive conformation accessible to both series. The synthesis of novel conformationally constrained analogues that might mimic the proposed bioactive conformation of these compounds, and the evaluation of their in vitro antiallergy activity form the subject matter of this report.

Animals↗
PubMed1999

Levels of dioxin-like compounds in sewage sludge determined with a bioassay based on EROD induction in chicken embryo liver cultures.

A bioassay for the detection of dioxin-like compounds was used to estimate levels in sewage sludge from Swedish sewage treatment plants (STPs). The sludge extracts were HPLC-separated into three fractions containing a) monoaromatic/aliphatic, b) diaromatic (e.g. polychlorinated biphenyls [PCBs], polychlorinated dibenzodioxins and polychlorinated dibenzofurans [PCDDs/Fs]), and c) polyaromatic compounds (e.g. polycyclic aromatic hydrocarbons [PAHs]). The bioassay, which is based on EROD (7-ethoxyresorufin O-deethylase) induction in cultured chicken embryo livers detected dioxin-like activity in all unfractionated extracts and in the di- and polyaromatic fractions of all sludge extracts, but not in the monoaromatic/aliphatic fractions. The levels ranged between 6 and 109 pg bio-TEQ/g sludge (d.w.). In sediment samples from rural lakes in Sweden, levels of about 5 pg bio-TEQ/g (d.w.) have been found. The polyaromatic fractions of the sludge samples were potent in the bioassay, probably due to various PAHs and other polyaromatics in the sludge. The levels of six PAHs that are screened for in the sludge at Swedish STPs accounted for only 3-10% of the observed EROD-induction by the polyaromatic fractions. Consequently, many other polyaromatic EROD-inducing compounds were present in the sludge. Inclusion of a biological test like the chicken embryo liver bioassay in the screening of sludge would improve the ability to detect the presence of bioactive dioxin-like compounds. A theoretical estimation of bio-TEQ concentrations in farm-soil following long-term application of sludge with bio-TEQ concentrations similar to those observed in this investigation indicated that the bio-TEQ levels in soil would increase very slowly over time. The chicken embryo liver bioassay proved useful in assessing levels of dioxin-like compounds in sewage sludge and it gives valuable complementary information to chemical analysis data.

Animals↗
PubMed2001

Natural and synthetic inhibitors of UDP-glucuronosyltransferase.

Glucuronidation is a major detoxification pathway in vertebrates. The reaction is catalyzed by a family of UDP-glucuronosyltransferases (UGTs) and involves conjugation of many endobiotic and xenobiotic substances with glucuronic acid, forming inactive water-soluble glucuronides. UGT prevents the accumulation of potentially toxic compounds and/or their subsequent bioactivation to more toxic intermediates, although biologically active glucuronides are also known. Impairment of UGTs may have important toxicological consequences. Substances found to inhibit or down-regulate UGT activity include endogenous compounds, a wide range of clinically used drugs, environmental contaminants, and natural toxic substances present in the diet. The development of selective, active-site-directed UGT inhibitors greatly enables the study of various UGT isoenzymes. A promising approach offers the design of transition-state analogs of the glucuronidation reaction.

Animals↗