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Search for "in vivo" in Full Text gives 292 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Oligonucleotide analogues with cationic backbone linkages
Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111
- bioactive agents. However, modifications of the nucleic acid structure are an essential prerequisite for their application in vivo or even in cellulo. The oligoanionic backbone structure of oligonucleotides mainly hampers their ability to penetrate biological barriers such as cellular membranes. Hence
An overview of recent advances in duplex DNA recognition by small molecules
Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93
- biological activities were thoroughly studied both in vitro and in vivo. One significant representative of this class is tallimustine (FCE 24517, TAM), which is a benzoyl nitrogen mustard derivative of distamycin characterized by an oligopeptidic pyrrolocarbamoyl framework ending with an amidino moiety [39
- a broad spectrum of in vitro and in vivo antitumor activities. Tallimustine retains the preference for A·T-rich regions in the minor groove that alkylates N3 of adenine in a highly sequence specific manner, thereby inhibiting the binding of transcription factors such as OTF-1 and NFE1 on specific AT
- structure–activity relationship. It has been observed that the number and position of pyrrole rings are crucial for antileukemic activity. The presence of pyrrole rings close to the alkylating BAM moiety is responsible for better cytotoxic activity both in vitro and in vivo, whereas a pyrazole ring in close
The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series
Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85
- -natural C-18 steroid containing cis junction of rings C and D [21][22]. This core-modified compound differs from its natural 13β counterpart not only in the configuration of C-13, but also its more flexible conformation. Poirier et al. investigated the in vitro and in vivo estrogenic activity of 3,17
On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site
Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80
- [120]. The two conjugates were subjected to stability tests and they showed slow drug release in human serum in contrast with nude mice that carboxylesterase enzymes are about 10 times higher [121]. Consequently, the two analogs were heavily evaluated in in vivo models in nude mice bearing various
- . The results demonstrated the stronger inhibition of AN-152 on the tumor with respect to the free DOX [126]. Similarly, in vivo experiments were conducted regarding AN-207 in nude mice bearing xenografts of MDA-PCa-2b prostate cancer cells, showing identical results like AN-152 [127]. Gründker et. al
- . evaluated the antitumor effects of AN-152 in vivo in human LHRH-R-positive HEC-1B endometrial and NIH:OVCAR-3 ovarian cancers, and in the LHRH-R-negative SK-OV-3 ovarian cancer cell line via intravenous injections [128]. The tumor volumes of HEC-1B and NIH:OVCAR-3 cancers were reduced significantly even
Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property
Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78
- synthetic route resulting in a higher yield, which might be relevant for larger scale synthesis needed for further in vivo studies. We show that the changes decrease the chemostability of the cyclic NGR moiety, resulting in the formation of isoAsp derivatives in higher amount. Among the new cyclic NGR
Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery
Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64
- reported on the identification of a novel daunorubicin–GnRH-III conjugate (GnRH-III–[4Lys(Bu), 8Lys(Dau=Aoa)] with efficient in vitro and in vivo antitumor activity. To get a deeper insight into the mechanism of action of our lead compound, the cellular uptake was followed by confocal laser scanning
- ) and human colon cancer cells (HT-29), is GnRH-III–[4Lys(Bu), 8Lys(Dau=Aoa)] (K2). Recent studies demonstrated that the butyrilation of the lysine in position 4 not only leads to an increased in vitro but also to an enhanced in vivo antitumor activity [29][30]. In order to achieve a better
Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing
Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32
- and some of them have been successful. Moreover, in the search for an alternative way to make efficient ON-based drugs, the general concept of prodrugs was applied to the oligonucleotide field. A prodrug is defined as a compound that undergoes transformations in vivo to yield the parent active drug
- binding site (miRNA masking) [8]. Although many ONs are under investigation for clinical use, several hurdles remain to be overcome for the exploitation of ONs as therapeutic compounds. Among the major limitations of unmodified ONs, poor stability in vivo, low delivery and lack of specificity to target
- 1958 [12], a prodrug is an agent that undergoes chemical or enzymatic transformations in vivo to yield the active parent drug. The prodrug approach is used to optimize the physicochemical properties of the drug and to improve its pharmacological and toxicological profile. Oligonucleotide prodrugs that
Synthesis of fluoro-functionalized diaryl-λ3-iodonium salts and their cytotoxicity against human lymphoma U937 cells
Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24
- suggested that antitumor drug candidates could be designed by further structural modification of these compounds 3. Moreover, with 3p exhibiting the greatest potency against U937 cells with comparably lower toxicity against AGLCL cells, further biological studies using 3p including in vivo evaluation should
Fluorogenic PNA probes
Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17
- into a measurable signal. Among several available modes of detection, fluorescence detection offers a number of distinct advantages, but mainly that it is relatively simple, selective, highly sensitive and can be used for real-time monitoring of the biological targets and even their interactions in
- vivo. For nucleic acids, the latter valuable information cannot be obtained by sequencing despite the tremendous advances in the field in recent years [1]. Accordingly, fluorescent oligonucleotide probes are still one of the most important tools not only for the detection of nucleic acids, but also
Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications
Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7
- conformations depending on conditions. Z-DNA, a GC-repeat rich, thermodynamically less preferred, left-handed helical conformation that is favored by cytosine methylation is known to form in vivo under negative supercoiling or high salt concentrations [64][65][66][67][68]. Circular dichroism is traditionally
Microfluidic radiosynthesis of [18F]FEMPT, a high affinity PET radiotracer for imaging serotonin receptors
Beilstein J. Org. Chem. 2017, 13, 2922–2927, doi:10.3762/bjoc.13.285
- invaluable insight into normal and abnormal brain function”. A further review by us focusing on 5-HT1AR overviewed a number of PET and SPECT tracers that have been tested in vivo with varying efficacy [2]. A few representative compounds which show the structures that have been tested as radiotracers are
- supersensitivity. Significant research has been directed at the differences between agonist and antagonist binding to 5-HT1A receptors in Alzheimer's disease [10] and this interest has led to the development of a high-resolution in vivo atlas for four of the human brain's serotonin receptors and transporters [11
Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays
Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271
- antibiotics. The fact that these cyclodextrin derivatives might be loaded with an antibiotic allows speculating that a possible antibiotic–CD complex could target the pathogen and in the meanwhile to bind and sequester extracellular DNA, inhibiting its role in vivo. Finally, a particular mention is deserved
Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate
Beilstein J. Org. Chem. 2017, 13, 2626–2630, doi:10.3762/bjoc.13.260
- Clement Ghiazza Anis Tlili Thierry Billard Institute of Chemistry and Biochemistry, Univ Lyon, Université Lyon 1, CNRS, 43 Bd du 11 novembre 1918, F-69622 Villeurbanne, France CERMEP-In vivo Imaging, Groupement Hospitalier Est, 59 Bd Pinel, F-69003 Lyon, France 10.3762/bjoc.13.260 Abstract Herein
Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling
Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242
- numerous bacterial terpene cyclase genes [2][3]. Both in vitro and in vivo approaches involving recombinant enzymes are commonly pursued for their functional characterization [4]. Care must be taken, however, in interpreting the results of these analyses, as the products of terpene cyclases are often
Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes
Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238
- desulfoclethramycin (1b) and clethramycin (1a) in vivo raised the question of whether there is a preferred or even obligatory order of events in the late-stage tailoring of the mediomycins in S. mediocidicus. In order to resolve this question we sought to characterise the putative sulfotransferase encoded by the
- (smala2697, or its counterpart from S. mediocidicus (medi5536). In each case, co-production of 1a was fully restored (Figure 2C and 2D). These in vivo results together establish that Medi4948 is capable of deprotection of both 1a and 1b and that the sulfotransferase SMALA_2697 (or Medi5536) is responsible
Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole
Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232
- time, the 1,2,3-triazoles became the heterocycle of choice in drug discovery, due to their favourable pharmacokinetic and safety profiles, hydrogen-bonding capability, moderate dipole moment, rigidity and stability under in vivo conditions [5][6]. Also, the ability of 1,2,3-triazoles to act as amide
Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines
Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224
- showed cytotoxicity even in the dark. This result suggests that the trifluoroethoxy group reduces the cytotoxicity of the phthalocyanine. Subsequently, an in vivo investigation was also conducted. Chicken embryos transplanted with cancer cells were treated with PDT by a cyclodextrin conjugate and proved
Phosphonic acid: preparation and applications
Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219
- K26 6) [45] or the anti-osteoporosis compounds alendronate (7) [46] and zoledronate (8) [47] (Figure 3A). In some cases, the bio-active phosphonic acid is generated in vivo from a phosphonate pro-drug [48] as exemplified by the formation of 10 from 9 which permits to improve the pharmacokinetic
Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?
Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206
- to improve their in vivo bioavailability and stability. This progresses empowered the potential of therapeutic peptides, suggesting a production surge in the future. Besides this high potential, actual peptide production techniques suffer from major environmental issues [4][5][6]. Indeed, large
Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides
Beilstein J. Org. Chem. 2017, 13, 2078–2086, doi:10.3762/bjoc.13.205
- conformational restriction has led to the enhancement in target selectivity and in vivo stability of the nucleoside-based drug candidates. One of the important precursors for the synthesis of different types of bicyclonucleosides is 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribofuranose. The synthesis of the
The chemistry and biology of mycolactones
Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159
- death, mainly via apoptosis, is observed in vitro and in vivo [32][33][82]. It is worth mentioning that in certain cell types, e.g., adipocytes, cell death via necrosis is dominant over apoptosis [83]. The most commonly used cells to study the cytopathogenicity of mycolactones are murine L929
- 8000 host genes identified the angiotensin type II receptor (AT2R) as the molecular target of mycolactone, which was confirmed by genetic knockout in vitro and in vivo and by chemical inhibition. In a competition binding assay mycolactone was able to displace the potent radiolabeled agonist [125I
- crystallography, would be highly appreciable. Finally, we also demonstrated the key role of mycolactone-triggered Bim-mediated apoptosis in vivo. To this end, the food pads of wild-type (WT) and homozygous Bim and Fas knockout mice (Bim−/− and Fas−/−) were infected with M. ulcerans. Intriguingly, WT and Fas
2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization
Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148
- -cell catalysts. Cells usually show increased stability towards cosolvents, pH and elevated temperatures [22][23]. A recent example in the field of artificial metalloenzymes was shown by Ward and co-workers, who used an artificial metathease in an in vivo approach. These first attempts are promising to
Grip on complexity in chemical reaction networks
Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147
- dynamics could be achieved by transcription and translation processes. Dissipation arises from an approximated constant supply of nucleotides, amino acids, and enzymes among other cellular machinery (see Figure 4d) [92]. Arguably, the ability to rationally assemble test tube CRNs lags behind that for in
- vivo systems due to difficulties faced in mimicking such cellular composition [93]. Consequently, in molecular “circuits” based on DNA as building blocks, certain reaction rates are often not known, cannot be known, or cannot be tuned easily. Blueprint for the construction of chemical complex systems A
An improved preparation of phorbol from croton oil
Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133
- , Australia 10.3762/bjoc.13.133 Abstract Background: Croton oil is the only commercial source of the diterpenoid phorbol (1a), the starting material for the semi-synthesis of various diesters extensively used in biomedical research to investigate cell function and to evaluate in vivo anti-inflammatory
- this chemotype. Croton oil is used as a reference for in vivo anti-inflammatory assays, like the mouse-ear erythema assay, and it is tempting to suggest that the notoriously poor-reproducibility of the data from this assay [23] might be related also to differences in the composition of croton oil
Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors
Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126
- is the inversion of the configuration at C-13, which is accompanied by drastic conformational change for the overall molecule resulting from the cis junction of rings C and D [2]. The influence of inversion of the configuration at C-13 in 3,17-estradiols on their in vivo and in vitro estrogenic
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