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Search for "toxicity" in Full Text gives 364 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells
Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11
- (Ewing`s sarcoma), MDA-MB-468, MDA-MB-231 (both breast cancer) and 184B5 (normal breast; chemically transformed) were investigated. As hoped, the toxicity of tubugi-1 was masked, with IC50 values decreased by ca. 1,000-fold compared to the free toxin. Due to intracellular linker cleavage, the cytotoxic
- very potent, mostly cytotoxic drug molecules while avoiding or at least limiting the off-target toxicity that would be characteristic for the stand-alone cytotoxic drugs. Currently, four therapeutic ADCs are approved, e.g., with brentuximab vedotin and trastuzumab emtansine as the first ones on the
- cells’ membrane by unspecific, receptor-independent pathways, not discriminating between normal and transformed cells. For that reason it is very difficult to adjust a practicable therapeutic window for these toxins. All the more, it is important to mask the high toxicity of tubulysin A and tubugi-1
Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand
Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3
- lower toxicity, air sensitivity and lower costs [34]. A huge repertoire of organocatalyzed reactions have been published in recent years with high efficiencies and selectivities [29][33][35][36][37][38][39]. Proline as a natural amino acid is a perfect example of an organocatalyst. Both enantiomers are
Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents
Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284
- antibiotics. Although cisplatin is highly toxic for humans upon systemic exposure, a low toxicity was demonstrated with topical treatment. This indicated that higher-than-minimal inhibitory concentration (MIC) doses of cisplatin could be topically applied to treat persistent and recalcitrant P. aeruginosa
- effective than the clinically used antibiotic tobramycin in eradicating biofilms. Although cisplatin is highly toxic for intravenous applications, we showed that it has low toxicity when applied topically to wounds, as 25 mM (0.75 mg mL−1) did not have adverse effect on wound healing. This meant that higher
- doses (5–10 × MIC) of cisplatin could be safely used for topical applications. Given the low topical toxicity of cisplatin, it may be utilized as an attractive therapeutic agent for prevention and treatment of P. aeruginosa biofilm infections. Materials and Methods Bacterial strains and culture media
Organometallic vs organic photoredox catalysts for photocuring reactions in the visible region
Beilstein J. Org. Chem. 2018, 14, 3025–3046, doi:10.3762/bjoc.14.282
- chemistry. Thanks to the development of photoredox catalysts of polymerization, a drastic reduction of the amount of photoinitiators could be achieved, addressing the toxicity and the extractability issues; high performance initiating abilities are still obtained due to the catalytic approach which
- catalysts For some specific applications, it can be essential to develop metal-free systems because of potential toxicity, storage stability or bioaccumulation of metal for example. Organic photoredox catalysis has been largely studied in the past few years and is the topic of many reviews [17][40][45][49
- conditions tested. The choice of the photoredox catalyst has also to be done regarding the application: final toxicity, choice of the device to perform the polymerization (light irradiation, under air or not…), price of the formulation, etc. For both free radical and cationic polymerizations, only a very
Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics
Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267
- -positive pathogens such as methicillin-resistant S. aureus and S. pneumoniae but also Gram-negative bacteria strains such as P. aeruginosa and A. baumannii (MIC ≤ 3 μg/mL and ≤51 μg/mL, respectively) [95]. In spite of the efficiency of the bis-aminoguanidine derivative 42, unfortunately, its toxicity was
- not display toxicity to mammalian cells. Even though the NusB/NusE interaction is still in its infancy, and further investigations are needed to both elucidate off-target effects and apparent preferential inhibitory activity against Gram-positive pathogens, the identification of promising small
An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes
Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253
- organic chemistry [12][13][14][15][16]. On the other hand, to reduce the toxicity and increase the efficiency, sulfonic acids are heterogenized on the various solid supports [17][18][19]. In fundamental, heterogeneous catalysis is interminably fascinating and perennially novel [20]. The few reports on
Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer
Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244
- malignancy [23] and inflammatory diseases. They are also utilized for targeted drug delivery [24][25] of therapeutics to avoid any off-site toxicity to normal and healthy cells. Unfortunately, strategies to construct diagnostic and therapeutic chemical tools consisting of a polypeptidic spacer, a homing
- would cause unwanted toxicity and inaccuracy in the biological study. The SH group present in the bioconjugate handle or chelating core of compound 13 and 17 can be utilized for the attachment of drugs [47], nanomaterial and radionuclide for therapeutic purposes. This added advantage makes the
- non-specific uptake. The specificity of bioconjugates is indispensable to prevent collateral damage and toxicity to healthy cells when the chelating core is tethered to deliver radionuclides or cytotoxic drugs. The confocal microscopic images in Figure 3, panel (ii) shows the uptake of chelating DUPA
Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections
Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239
- acute toxicity/virulence are likely to be successful as future therapies against the impending threat of highly antibiotic-resistant pathogens. In some cases, it was already shown that virulence blockers act synergistically in combination with antibiotics, for example against P. aeruginosa biofilms [44
Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells
Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235
- vascular endothelial cadherin (VE-cadherin) is the major structural component of endothelial AJ with a pivotal role in endothelial barrier integrity. LasB protease released by P. aeruginosa during infection determines VE-cadherin cleavage and facilitates type III secretion system toxicity in endothelial
Learning from B12 enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis
Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232
- environmental pollution, resulting in very chronic diseases [78]. However, it was known that the toxicity of organic arsenics is generally much lower than inorganic ones. For example, the acute toxicity of arsenobetaine (AB) is about one three-hundredth that of arsenic trioxide [79]; trimethylarsine oxide (TMAO
- ) that is an intermediate in the synthesis of AB also has lower toxicity than inorganic arsenics. Moreover, inorganic arsenics could be converted to methylated arsenics via human or animal metabolism involving a methyltransferase and a reductase [80][81][82]. Thus, biomimetic transformation from
Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids
Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226
- ; Introduction The application of more selective, targeted drugs has become increasingly important in the treatment of tumors, where the use of chemotherapeutics with low therapeutic index is restricted by the adverse events coming from the toxicity of these drugs to normal cells [1]. One of the most promising
- (Dau=Aoa) ~ GnRH-III(Dau=Aoa). While there were no significant differences between [4Lys(Ac)]-GnRH-III(Dau=Aoa) and [4Lys(Bu)]-GnRH-III(Dau=Aoa) in terms of long-term (48 h) toxicity, the conjugate with butyryl side chain proved to be more effective after 6 h-long exposure. It seems that the short-term
Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues
Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207
- applied in pest control and crop protection due to their broad pest spectrum, high insecticidal activity, low environmental impact, and low toxicity to non-target species [4]. So far, more than 24 natural spinosyns and 800 semi-synthetic spinosyn analogues have been obtained and characterized, and their
- codling moth (Cydia pomonella), a major pest of pome fruits, tobacco budworm, cotton and vegetable crops [8]. Like spinosad, spinetoram elicits toxicity in the pest species via a neurotoxic mode of action. Although the exact mechanism of action has yet to be characterized, it is hypothesized that the
- a broad-pest spectrum and crop-uses, spinosad and spinetoram are both environment- and human-friendly. In addition, spinosad and spinetoram show high specificity to target insects and low toxicity to both mammals and beneficial insects [11]. Therefore, spinosad and spinetoram were successively
The enzymes of microbial nicotine metabolism
Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204
- Paul F. Fitzpatrick Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX, 78229, USA 10.3762/bjoc.14.204 Abstract Because of nicotine’s toxicity and the high levels found in tobacco and in the waste from tobacco processing, there is a great
Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine
Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198
- specific structures and interesting host–guest properties [21][22][23][24][25][26][27][28][29][30][31][32]. Water-soluble pillar[n]arene derivatives, especially those containing carboxylato moieties, showed low cell toxicity and good biocompatibility, and have been applied in biomedical applications such
A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines
Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196
- ]. Whilst Cl2 gas is atom efficient it is difficult to handle, with associated toxicity, and the acid byproduct which leads to N-chloramine hydrolysis [16]. On the other hand, N-chlorosuccinimide or chloramine-T are commonly employed, being commercially available, stable and straightforward to handle
Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry
Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179
- achieve this as well. This is the most energetically sustainable way possible to carry out a chemical transformation. A result of this use of the energy of photons is that photochemical transformations often require fewer and/or less reactive (which correlates to toxicity and environmental impact
Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3+ + 2]-cycloaddition/rearrangement reactions
Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155
- examples of such clinically drugs having enhanced effects on the neurotransmitter γ-aminobutyric acid (GABA) at the GABAA receptor and low toxicity (Figure 1) [15]. Although 1,4-benzodiazepines are widely prescribed medicines, side effects like drowsiness, drug resistance, addiction and withdrawal
Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes
Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154
- used in organic synthesis since the 1990s, due to their stability, low toxicity and mild reaction conditions [1][2][3][4][5][6][7][8][9][10]. Structurally, they always adapt a distorted trigonal bipyramidal geometry in which the less electronegative aryl ring and two lone pairs of electrons are
Natural and redesigned wasp venom peptides with selective antitumoral activity
Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144
- and to avoid toxicity towards normal host cells. Antimicrobial peptides (AMPs) are produced by the innate immune system of virtually every organism on Earth. These agents represent promising anticancer candidates since, in addition to their activity vs bacteria [1], viruses, parasites [2][3][4][5][6
- . Furthermore, Dec-NH2 and its analogs were hemolytic at concentrations above their MIC values for the different microorganisms studied [9][10]. MTT cytotoxicity assays MTT assays were performed to determine the toxicity of designer peptides against MCF-7 cancer cells and MCF-10A normal cells. MCF-10A cells
- analogs after 2 and 24 h of exposure to MCF-7 cancer cells. Experiments were done in triplicate. MTT assays evaluating the toxicity of Dec-NH2 and its derivatives towards MCF-10A normal cells after 2 and 24 h. Experiments were performed in triplicate. Cell death analysis using flow cytometry. Dot plot
β-Hydroxy sulfides and their syntheses
Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143
- (-CH2X), alkoxy (-CH2O), aryloxy (PhO), aryl (Ph) and alkyl (-CH2) substituents on the epoxide. The virtues of this protocol are the low cost and ready availability of NBS, its moisture and air stability as well as low toxicity. The reaction is characterized by short reaction time, good to high product
- host–guest complexes by non-covalent bonding [64]. This mode of catalysis is similar to the way enzymes mediate biochemical reactions [64]. The use of water as a solvent and the non-toxicity of the cyclodextrin catalyst make the method attractive. This method, like the previously reported protocols, is
Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells
Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136
- compare the influence of sequence modification, the presence or absence of a spacer as well as the type of spacers on toxicity. Disulfide dimers were also developed based on conjugates 4, 6 and 8, resulting in compounds 9, 10 and 11. Four conjugates with two identical (Dau) or different (Dau and Mtx) drug
- concentrations (10−7 and 10−6 mol/L). In contrast, these conjugates showed significantly lower toxicity at 10−7 mol/L, but a slightly higher toxicity at the highest concentration level (10−6 mol/L) on cardiomyocytes in a long-term experiment. It is worth mentioning that none of the compounds showed toxicity on
- cardiomyocytes and HUVEC endothelial cells in the long-term study. The oxime bond-linked Dox conjugate (3) showed significantly lower toxicity on both cell types, while conjugate 2 had a similar concentration-dependent toxicity to that of the ester bond-linked conjugates on endothelial cells. The toxicity of the
Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions
Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116
- peptides when incubated with MCF-7 cells up to a concentration of 100 μM. Also after treating HeLa cells with the peptides up to a concentration of 50 μM, no significant toxicity could be observed for sC18*, N50, N50-sC18* and NrTP. Besides N50, all other peptide sequences did lower the amount of viable
- cells to an amount of around 80% at higher concentrations. For sC18* the results are in very good agreement to our former studies, in which we also examined the toxicity in other cell lines, like human epithelial kidney cells (HEK-293) and human colorectal adenocarcinoma cells (HCT-15) [19][20]. Notably
A survey of chiral hypervalent iodine reagents in asymmetric synthesis
Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107
- application due to their reduced toxicity, ready availability and lower costs as replacement for transition metals leading to several “metal-free” like chemical transformations. The ongoing demand of modern synthetic chemistry for the development of catalytic enantioselective C–C bond formation reactions
Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis
Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97
- . Hypervalent iodine reagents have drawn researchers’ considerable attentions due to their versatile reactivity, low toxicity, ready availability, environmental friendliness, and regenerability [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Our group has dedicated to the peptide synthesis
- . Compound 6 was subsequently oxidized with NaOCl/HCl to obtain FPID in 90% yield. Cyclic peptides, an important kind of peptides, possess several favorable properties such as target selectivity, good binding affinity and low toxicity, which make them attractive candidates in the development of therapeutics
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
- high binding affinity to B-DNA duplexes, several groups have designed various structural analogs of Hoechst 33258 in order to achieve a better sequence-specific DNA binder with reduced toxicity [114]. Yang et al. reported a series of novel symmetrical bisbenzimidazoles as DNA minor groove binders. A
- promyelocytic leukemia cells) tumor cell line and 0.58 μM for U937 (Human leukemic monocyte lymphoma cells) tumor cell line with reduced toxicity in comparison to paclitaxel and 5-FU [116]. Ivanov et al. reported two different sets of strong minor groove binders, derived from well-known DNA minor groove binder
- charged phosphates, thereby stabilizing the complex through the formation of cross-links between neighboring duplexes [83]. However, due to intrinsic toxicity, various structural analogs of pentamidine were designed over the years by replacing the ether linkage with bis-amide 61 [125], introducing
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