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Search for "in vivo" in Full Text gives 292 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Anthelmintic drug discovery: target identification, screening methods and the role of open science
Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105
- against A. ceylanicum adults than C. elegans assays (lower false negative rate). This works lead to the testing of four compounds with in vitro activity in an in vivo A. ceylanicum hamster infection model – sulconazole (13), econazole (14), pararosaniline (15) and cetylpyridinium chloride (16) (Figure 3
- basis for finding compounds that are anthelmintic in vivo but do not cause paralysis, perhaps involving aspects of the interaction with the host, interfering with the secretion of proteins, or other ways of damaging the worm [146]. They are also useful for understanding in more detail the mechanism of
- action of anthelmintic compounds, since it has been recognised that we do not fully understand how many anthelmintics work – for example the concentrations of macrocyclic lactones that paralyse worms in vitro are much greater than the concentration achieved by effective doses in vivo [147]. Several
Fluorinated phenylalanines: synthesis and pharmaceutical applications
Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91
- . demonstrated its inhibitory activity of gastrin-stimulated growth of pancreatic cancer both in vitro and in vivo studies [110] (Figure 4). 5.2.3. Dual CCK1/CCK2 receptor antagonists: Johnson & Johnson identified compound 182 as a dual CCK1/CCK2 receptor antagonist with desirable pharmacologic properties [51
Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules
Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68
- of known, in vivo effective substances but also for designing chemically modified analogs as valid alternatives for further therapeutic agents. Keywords: bioactive compounds; enyne metathesis; ring-closing metathesis; ruthenium catalysts; tandem reactions; Introduction Alkene and alkyne metathesis
Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition
Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59
- alternative treatment options for neuroblastoma, some patient cohorts who are considered high risk at the time of diagnosis face poor prognosis [24][25]. Recent studies indicated that HDAC8 inhibition induces differentiated phenotypes and reduces neuroblastoma growth in vitro and in vivo with few adverse
- panobinostat against HDAC8 have been shown to be 277 nM [11]. In vivo studies measuring the IC50 values of panobinostat have also been performed, however, since panobinostat is a pan-DAC inhibitor it has been difficult for researchers to specifically correlate its IC50 value for HDAC8 in a physiological system
Opening up connectivity between documents, structures and bioactivity
Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54
- connectivity is out of scope for this article. Bioactivity: This covers a wide spectrum of assay read-outs but with a focus on in vitro, in cellulo, in vivo and in clinico. Ideally this should also include low or inactive analogues which are crucial for SAR elucidation but documents are (understandably) biased
- 22833565 with 1040 Mw) has been annotated (even though the sodium salt is the active form in vivo). Note also that while formally “P” in the heparin case is SERPINC1 (ATIII) the mechanism is an indirect one involving the activation of binding to F2 (activated thrombin) for inhibition. Another problematic
- ≈25000 papers. Despite being the smallest of the three, GtoPdb shows proportionally more unique PMIDs. This is substantially due to the curators adding additional references into the SID records beyond those from which the binding data were extracted (e.g., in vivo and clinical reports published after
p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies
Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33
- carbamates are able to release amines which in in vivo action may imbalance the pH of the tissues, and still retain the ability to create radicals. The same applies to hypoxic environments and anaerobic conditions. Finally, with this study, we have shown that oxime carbamate derivatives have the potential to
Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations
Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26
- agents in vivo. The yields were calculated as radiochemical yields (RCYs): these yields are measured from the values of decay-corrected radioactivity. This is analogous to the concept of a regular yield but calculated for the radionuclide. Technically, the RCY is connected to the quantity of
Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo
Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14
- cytoskeleton research. Additionally, as the hemithioindigo scaffold allows photoswitchable bioactivity for substituent patterns inaccessible to the majority of current photopharmaceuticals, wider adoption of the hemithioindigo scaffold may significantly expand the scope of cellular and in vivo targets
- future in vivo studies. We also noted that the para-hydroxy HITubs featured ca. 30% residual (Z)-HITub at PSS λ = 450 nm in cell-free measurements, and that for HITub-2–4, the PSS isomer mixture's cellular cytotoxicity at that wavelength was on average 3.3-fold lower than the cytotoxicity of the
Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos
Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6
- embryotoxicity of dithienylethene-modified peptides upon photoswitching, using 19 analogues based on the β-hairpin scaffold of the natural membranolytic peptide gramicidin S. We established an in vivo assay in two variations (with ex vivo and in situ photoisomerization), using larvae of the model organism Danio
- , (iii) demonstrate photoswitching of the whole-body toxicity for the dithienylethene-modified peptides in vivo, (iv) re-analyze previous structure–toxicity relationship data, and (v) select promising candidates for potential clinical development. Keywords: diarylethene photoswitch; gramicidin S
- plasma stability in vivo, limited understanding of their mechanisms of action, and high in vivo toxicity. The former two drawbacks are being adequately resolved [9] (e.g., by modifying the peptide backbone [10], macrocyclization [11], or by use of unnatural amino acids [12]), and mechanistic
Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives
Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296
- azobenzenes – have recently been found to exhibit photoswitching properties suitable for in vivo use [8][9][10]. Typically, the formation of azonium ions from aminoazobenzenes occurs at pH < 3.5 [11][12], however, the pKa of the trans-azonium ion 1 is ca. 7.5 in aqueous solution (Figure 1) [9][10]. The
Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering
Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283
- ent-kaurenoic acid (27 and 28, respectively, Figure 7b) [41]. Characterization of CYPs is typically achieved by in vitro or in vivo studies. E. coli is the most popular host for obtaining proteins for in vitro studies, and proper selection of a redox system is usually the obstacle to reconstitute CYP
- activity. Substrates for in vivo studies are either added to the culture or supplied by coexpression of upstream enzymes in the heterologous hosts. If E. coli is selected as the host, coexpression of a redox system is required, as E. coli does not harbor any CYPs [88]. In comparison to TCs, tailoring genes
Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum
Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281
- (Figure 1A). It is thus conceivable that PpolyTPS4 is responsible for the formation of these three compounds in vivo. PpolyTPS1 produced also α-muurolene, however, the in vitro product profile was dominated by other sesquiterpenes that were not detected in the headspace of P. polycephalum. Nonetheless
- incomplete transcriptome and genome information, but contribute to the in vivo biosynthesis of linalool. It is interesting to note that only PpolyTPS1 and PpolyTPS4 are closely related to TPSs of dictyostelid social amoebae whereas PpolyTPS2 and PpolyTPS3 are closely related to bacteria TPSs (Figure 4
Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission
Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274
- activation with cycles of violet and green light. Due to the very long-lived metastable cis configuration, 4FAB in vivo use could be of great promise for long term biological studies. Further chemical functionalization of this 4FAB probe with a maleimide functionality allowed clean cross-linking with
- regular AB-based photoswitch called "MAHoCh" [16]. The MAHoCh probe was originally designed [16] to activate nicotinic acetylcholine receptors in vivo. However, it was found that the trimethylammonium (TA) head group blocked acetylcholine binding when the photoprobe was cross-linked to the channel near
- the electron donor effect of the methylene substituent decreases the thermodynamic stability of the cis form compared to that report by Hecht [13], protein conjugates of 1 would be highly stable in vivo over the course of a typical daily mouse behavioral experiment [15]. cis-MAHoCh has a significantly
An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent
Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271
- penetration is an essential requirement of the compound but would be an ideal peripherally restricted control. These data will contribute to the understanding of drug levels of 1 to overlay with appropriate in vivo efficacy endpoints, i.e., the PK-PD relationship. The identification of a suitable analogue of
- to just 7 steps from 16 and improves the overall yield to 40–50 %. Mouse pharmacokinetics for 1 Assessment of 1 in mouse liver microsomes (MLM) showed excellent metabolic stability (Cli 1.0 μL/min/mg protein) which predicts for low clearance in vivo. Binding to mouse plasma proteins (mPPB) was very
- high with percent unbound drug (fu) of just 0.1%; this mPPB value can be used to calculate free drug concentrations from measured drug levels in plasma taken during in vivo experiments. The high mPPB is entirely consistent with the physicochemical properties of 1 as a lipophilic acid (mw 300; cLogP 3.1
A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations
Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250
- dyes Cy5.5 and Alexa Fluor® 680 [23]. Moreover, silicon rhodamines demonstrated in in vivo imaging experiments excellent fluorescence properties and biostabilities [23] as well as exhibited high quantum efficiencies with high tolerance to photobleaching [24]. A silicon rhodamine antibody conjugate
In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization
Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243
- ] and in vivo [8][9][10][11][12]. Manipulation of gene expression demonstrated therapeutic application – antisense chemistry [13]. Along these lines, photopharmacology [14][15] is an emerging field that highlights the importance of reversible photocontrollable drugs in tomorrow’s medicine, but
- been employed. In vivo application demands the development of a new generation of artificial agents to target DNA/RNA-associated processes. These compounds must be able to maintain their specificity and effectivity while still being nuclease resistant, nontoxic and susceptible to light of tissue
- properties of PNA, they may become a promising alternative to overcome the current limitations of the available photoswitchable DNA- and RNA-based systems with potential for in vivo applications too. Only very few is known about the reversible hybridization of PNAs upon irradiation [34][35][36]. Besides
Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor
Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230
- -controllable “ON/OFF” working states. The OFF-state (one of the photoisomer or photocaged structure) “masks” the probe before reaching the target analyte, avoiding unwanted interactions with other abundant species in the “working zone”, or unnecessary consumption with analyte in nontargeted locations during in
- vivo/intracellular transport [18][19][20]. 2) A dynamic ON/OFF fluorescence signal is generated for reversible imaging of a targeted analyte (termed as “double-check”), which can facilitate a better discrimination of the analyte signal from the background interferences [9][10][11]. As a result, more
Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses
Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221
- nanocrystals [6]), widely used for imaging live cells, for in vivo imaging and diagnostics [7]. Even if the properties of quantum dots have been compared with those of classical organic fluorophores [8], organic fluorophores having giant TPA properties are far less common [9], although there are noticeable
- use concerned in vivo imaging with some of the dumbbell-like dendrimers. The second generation of the dendrimer shown in Figure 9 was injected to a rat and the two-photon imaging of the vessels of the living rat olfactory bulb could be obtained [56]. The other dumbbell-like dendrimer shown in Scheme 5
- surface of the dendrimers incorporating TPA fluorophores inside their structure has led to interesting properties in biology. Indeed, some of these dendrimers have been used in vivo as tracers for imaging blood vessels of rats and tadpoles, others have been used for determining phenotype of cells, for
Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors
Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214
- the biological activity of small molecules in vitro or in vivo comprises numerous opportunities for example in the elucidation of biochemical pathways or the reduction of systemic side effects in drug therapy. Molecular photoswitches, i.e., compounds that undergo changes in their geometry and
Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products
Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202
- Tvi09626 with other characterised terpene synthases. Six clades are marked with different colours and Tvi09626 is labelled in red in Clade V. Percentages indicate branch support based on 1,000 bootstrap replicates. GC–MS chromatogram of products in vivo (I), in yeast YZL141 (II), in vitro Tvi09626 with FPP
Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)
Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190
- available for most of the analytes. For this reason, feeding experiments (in vivo labeling) were carried out using the stable isotope-labeled precursors [5,5-2H2]-1-deoxy-ᴅ-xylulose (d2-DOX) and [6,6,6-2H3]-(±)-mevalonolactone (d3-MVL) to clearly identify the volatiles. Based on the recorded mass spectra of
- advantages of multidimensional gas chromatography with those of in vivo labeling. In vivo labeling makes it possible to identify compounds for which authentic standards are not commercially available, which applies to the majority of compounds found in plant foods [18]. We performed feeding experiments on
- and Tantillo, d9-α-ylangene with m/z = 213 should have been detected after in vivo labeling using [6,6,6-2H3]-(±)-mevalonolactone (d3-MVL) as precursor. At this point it should be mentioned that biosynthetic pathways in organisms can differ and computational studies only bear on the intrinsic
Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides
Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174
- synthesized and biologically evaluated [19][20][21]. The best adjuvant activity in experiments in vivo showed the ManAdTP derivative (Figure 2) which has a ᴅ-configuration at the (adamant-1-yl)glycine moiety and (R)-configuration at the hydroxyisobutyryl linker. Its activity was higher than PGM that was used
- with derivatives lacking the adamantane moiety. Immunostimulating properties of synthesized derivatives were assessed in vivo using ovalbumin as an antigen. Results and Discussion Design Desmuramyl peptides enter into the cell by passive absorption and this process depends on lipophilicity [25
- the adjuvant activity in experiments in vivo [20][21]. Two series of manno-conjugates were prepared: (i) derivatives with glycolyl linker and (ii) the ones with (R)-hydroxyisobutyryl linker which is present in the parent ManAdTP. The glycolic linker was introduced due to the fact that N-glycolyl
Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif
Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144
- -OCF3 substituent is not directly metabolised, however, the sulphur associated with the -SCF3 group is susceptible to in vivo oxidation. Tiflorex, an appetite suppressant, toltrazuril, a coccidiostat used as an additive to poultry feed, and SKA-19, an anticonvulsant as shown in Figure 1, are three such
Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response
Beilstein J. Org. Chem. 2019, 15, 1394–1406, doi:10.3762/bjoc.15.139
- targeted therapy in vivo [27]. These biomedical applications depend on the fine set-up of receptor–dye complexation. In this work, we comprehensively investigated the complexation behavior of GC5A with a series of luminescent dyes. Their complexation-induced photophysical alternations were comparatively
- , indicating a tentative PET quenching mechanism, similar to the aforementioned ACQ examples. The data was well fitted by a 1:1 binding model, giving a Ka value of (1.4 ± 0.1) × 106 M−1 (Figure 3b, Table 1). Recently, such host–guest reporter pairs have been applied in cell imaging and even imaging in vivo [16
- economy, sensitivity and interference. When expanding these supramolecular assay strategies to bioimaging in cells and in vivo, two-photon reporter dyes exhibit advantages of deeper tissue penetration, higher spacial resolution and reduced photodamage of tissue. In the field of photodynamic therapy
Phylogenomic analyses and distribution of terpene synthases among Streptomyces
Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115
- ). These exceptions may indicate horizontal gene transfer of the genes encoding for these enzymes. The sesquiterpene 7-epi-α-eudesmol synthase from S. viridochromogenes DSM 40736 has been chemically characterised in vivo by heterologous expression in E. coli BL21 and identification of the product in
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