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Search for "cytotoxic" in Full Text gives 294 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
N-Acylated amino acid methyl esters from marine Roseobacter group bacteria
Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276
- on the LuxR type receptors for AHLs in bacteria [23][24]. Other potential functions are antimicrobial or cytotoxic activity of the tested derivatives. Roseovarius sp. D12_1.68 showed antimicrobial activity against a Rhodobacteraceae sp. TL and antialgal activity against Skeletonema costatum while
- Loktanella sp. D3 showed no antagonistic activity [29]. This observation fits well with the detection of antimicrobial or cytotoxic NAVME 9 and NABMEs 7 and 8 only in Roseovarius sp. D12_1.68. Bacteria are known to produce acylated amino acids, although the number reported so far is small, including tyrosine
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
- successfully designed and demonstrated a novel continuous process for assembling targeting ligands, peptidic spacers, fluorescent tags and a chelating core for the attachment of cytotoxic molecules, radiotracers, nanomaterials in a standard Fmoc solid-phase peptide synthesis in high yield and purity. 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
- can be employed as potential theranostic tools by attaching macromolecules, cytotoxic warheads, radioactive tracers, nanomaterials etc., via the chelating core. Experimental Materials and methods H-Cys-2-ClTrt resin, Fmoc amino acids and amide coupling agents, reagents and solvents used in solid-phase
Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers
Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241
- [38]. HQNO acts through inhibition of complex III in the respiratory chain of bacteria and mitochondria of eukaryotes and, hence, it can be considered a general cytotoxic agent. DHQ, a shunt product of the PQS biosynthetic pathway, is important for P. aeruginosa virulence in a Caenorhabditis elegans
Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence
Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236
- known to display cytotoxic effects on diverse cancer cells by inducing a disturbance in the cell cycle and promoting apoptosis without affecting normal cellular proliferation [4][5]. In these latter cases, detailed structural criteria are still not available owing to little information about the mode of
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
- by all the tested conjugates. The modification of the GnRH-III in position 4 was accompanied by an increased cellular uptake, higher cytotoxic and cell adhesion inducer activity. By studying the cell movement of A2058 cells with a holographic microscope, it was found that the migratory behavior of
- approaches to diminish this kind of cytotoxic effects on healthy tissues is the employment of drug delivery systems directed specifically to cancer cells. The chemotherapeutic drug targeting is often based on the receptors for certain peptide hormones that are preferentially expressed by cancer cells. The
- utilization of these receptors for cancer cell targeting allows for minimizing the toxic side effects and producing high drug concentration selectively at the tumor site. In general, drug delivery systems consist of a targeting moiety in order to recognize a receptor on tumor cells and a cytotoxic drug
Studies towards the synthesis of hyperireflexolide A
Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185
- antifungal [2] and cytotoxic activities [3]. γ-Lactone-fused cyclopentanes are of vital importance in organic synthesis and are the most abundant substructures found in various naturally occurring molecules [4][5]. A cis-cyclopentane ring-fused γ-lactone is the key structural unit of many complex and
Synthesis of spirocyclic scaffolds using hypervalent iodine reagents
Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152
- compounds have been employed as important synthetic intermediates for the construction of biologically active molecules such as histrionicotoxins and the cytotoxic marine alkaloid fasicularin [84]. In 2010, Honda [85] reported the synthesis of isoquinoline alkaloids possessing spirocyclic framework using
- [121] reported the synthesis of various oxygen analogues of naturally occurring compound discorhabdin A starting from substrate 110 in few chemical steps. Discorhabdin A is an alkaloid that shows various biological activities including strong cytotoxic activity [122]. During the first step, starting
Synthesis and photophysical studies of a multivalent photoreactive RuII-calix[4]arene complex bearing RGD-containing cyclopentapeptides
Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150
- photophysical and photochemical characterizations of this Ru(II)–calixarene conjugate as well as the study of its photoreactivity in the presence of guanosine monophosphate have been achieved. The results show that the ruthenium complex should be able to perform efficiently its photoinduced cytotoxic activity
- cytotoxic activity, once incorporated into targeted cancer cells thanks to the multivalent platform. In cellulo studies are currently under investigation and will be reported in the near future. Experimental General: All the solvents and reagents for the syntheses were at least reagent grade quality and
Natural and redesigned wasp venom peptides with selective antitumoral activity
Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144
- residues are not major components of cell-penetrating peptides [32], which are typically cytotoxic, so we chose to synthesize a Trp-containing analog as well. The changes in the designed analogs led to slight differences in specific physicochemical features (Table 1), such as hydrophobicity, hydrophobic
- concentrations (≈100 μmol L−1). On the other hand, [Leu]8-Dec-NH2 did not present significant activity against MCF-7 cells when compared to the negative control (Figure 2), and intriguingly was cytotoxic towards normal MCF-10A cells even at the lowest concentration tested (25 μmol L−1, Figure 3). This
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
- in compounds with increased therapeutic efficacy. The objective of the present study was to examine the cytotoxic effect of anticancer drug–GnRH-conjugates against two essential cardiovascular cell types, such as cardiomyocytes and endothelial cells. Sixteen different previously developed GnRH
- cells on golden electrode arrays placed at the bottom of the wells. Slopes of impedance–time curves were calculated and for the quantitative determination of cytotoxicity, the difference to the control was analysed. Results: Doxorubicin and daunorubicin exhibited a cytotoxic effect on both cell types
- , at the highest concentrations tested. Doxorubicin-based conjugates (AN-152, GnRH-III(Dox-O-glut), GnRH-III(Dox-glut-GFLG) and GnRH-III(Dox=Aoa-GFLG) showed the same cytotoxic effect on cardiomyocytes. Among the daunorubicin-based conjugates, [4Lys(Ac)]-GnRH-III(Dau=Aoa), GnRH-III(Dau=Aoa-YRRL), {GnRH
Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)
Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132
- their macrolactone ring was assigned based on NOE and vicinal 1H NMR coupling constants and by calculation of a 3D model. Lanyamycin inhibited HCV infection into mammalian liver cells with an IC50 value of 11.8 µM, and exhibited a moderate cytotoxic activity against the mouse fibroblast cell line L929
- of this class, bafilomycin A1 (Figure 3) is a useful biochemical tool as it prevents the re-acidification of synaptic vesicles once they have undergone exocytosis [14]. Bafilomycins are also known to be cytotoxic, inhibitors of autophagy, active against Gram-positive bacteria, yeast and fungi
- (KB3.1), colon carcinoma cells (HCT-116), and glioblastoma (U87MG). It exhibited cytotoxic activity with IC50 values of 3.1 and 1.5 µM against L929 and KB3.1 cell cultures, respectively, while it was not active against the other cell lines according to the limits of the National Cancer Institute (active
Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials
Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127
- composites loaded with quercetin may show improved cytotoxic activity towards some human breast cancer cell lines [32], likely due to a synergistic action between the polyphenol nutraceutic guest molecule and triazole derivatives coming from the progressive disgregation of the co-polymer carrier. From 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
- -sC18* and NrTP-sC18* formed α-helices that showed amphipathic character with a clear hydrophilic and hydrophobic face (Figure 1C). This property might support the interaction with the plasma membrane. Cytotoxic profile of novel CPPs In the next step, the cytotoxicity profiles of the novel peptide
Oligonucleotide analogues with cationic backbone linkages
Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111
- . Fluorescence microscopy revealed a cytoplasmic localization of the oligonucleotide without accumulation in the nuclei. This indicated an endocytotic uptake mechanism with (at least partial) retention of the material in the endocytotic vesicles. No unspecific cytotoxic effect of the guanidinylated
Novel unit B cryptophycin analogues as payloads for targeted therapy
Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109
- potential for chemotherapy. Since targeted therapy provides new perspectives for treatment of cancer, new potent analogues of cytotoxic agents containing functional groups for conjugation to homing devices are required. We describe the design, synthesis and biological evaluation of three new unit B
- glycol spacer with a terminal azide results in a complete loss of activity. Docking studies of the novel cryptophycin analogues to β-tubulin provided a rationale for the observed cytotoxicities. Keywords: cryptophycin; cytotoxic agents; novel payloads; tubulin inhibitors; tumour targeting; Introduction
- not better than its parent. In recent years the targeted delivery of cytotoxic agents has emerged as a highly promising method to tackle selectivity issues [36][37][38][39][40]. Cryptophycin-52 and many analogues lack an addressable group to conjugate the toxin to a homing device. For this reason, new
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
- ][40]. The benzoyl nitrogen mustard (BAM) to the formyl end of the distamycin acts as an alkylating moiety whereas the distamycin framework acts as a DNA binding domain. Therefore, due to the installation of the alkylating moiety, TAM has higher cytotoxic activity in comparison to distamycin, and shows
- of these classes of molecules including the amidine modification. In addition, a novel class of cytotoxic MGBs comprising of α-bromo or chloroacrylamide moieties linked to distamycin were identified. Among all different synthetic analogs, brostacillin (PNU-166196, Figure 3) was found to be a potent
- 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
Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines
Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88
- siderophore antibiotic D-fluviabactin, the cytotoxic agent westiellamide, the antifungal macrodiolide leupyrrin A1 and the antitumour compound BE-70016 (Figure 1). In addition, synthetic polymers based on the 2-oxazoline building block constitute versatile platforms for a range of biomedical applications
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
- . The general architecture of PDCs consists of three building blocks: the tumor-homing peptide, the cytotoxic agent and the biodegradable connecting linker. The aim of the current review is to provide a spherical perspective on the basic principles governing PDCs, as also the methodology to construct
- intervention, radiation and chemotherapy. Drugs used for this purpose are inevitably cytotoxic in order to eliminate cancer cells, but they lack selectivity that could be developed through targeting malignant cells (Figure 1). Due to the uncontrolled peripheral toxicity, anticancer drugs usually kill healthy
- , occurring via urine. Therefore, most conventional cytotoxic agents applied in chemotherapy lack optimum pharmacokinetic properties (ADME) and thus are not very effective to treat malignancies. Moreover, despite the intensive research to construct new cytotoxic drugs, survival rates in most cancers remain
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
- selectivity to CD13+ cells. However, the cellular uptake and cytotoxic effect of Dau=Aoa-GFLGK(c[NleNGRE]-GG-)-NH2 was higher in comparison to the control especially on HT-29 cells. Therefore, this conjugate is more suitable for drug targeting with dual targeting property. Keywords: antitumor activity; drug
- characterization of novel cyclic NGR peptides and their corresponding NGR-drug conjugates. Special attention was paid on the chemostability and in vitro biological activity of the compounds [17][18]. Daunomycin (Dau) was used as cytotoxic agent, attached to the NGR-derivatives via oxime linkage. The prepared
- conjugates revealed substantial in vitro cytostatic/cytotoxic effects. Our results indicated that the conjugates had an antitumor effect against both CD13+ HT-1080 cells and CD13− (but integrin receptor positive) HT-29 human colon cancer cells. Moreover, we showed that the toxicity and the selectivity of the
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
- , 9Pro-EA] and triporelin [6D-Trp], which are used as pharmaceutical peptides to treat inter alia hormone dependent prostate and/or breast cancer [7]. Since the mid-1980s cytotoxic GnRH-I derivatives were developed and investigated to treat tumor cells [4][5][8][9]. Anthracyclines such as doxorubicin
- cellular uptake and the subcellular localization of the drug or the drug bioconjugates [13][14]. It is well known from the literature that anthracyclines accumulate in the nucleus, in that manner they also act as DNA stains [14][15]. The first cytotoxic GnRH-I derivative, which was investigated in
- the release of the cytotoxic agent within the tumor cell. During clinical trials, only mild side effects were observed which are caused by premature drug release [17]. The receptor mediated uptake of zoptarelin has been investigated by blockage of GnRH receptors using an excess of the GnRH-I
Mannich base-connected syntheses mediated by ortho-quinone methides
Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43
- active zwitterionic species via an o-QM intermediate. Dimmock et al. subsequently examined the cytotoxic activity of phenolic azobenzene Mannich bases [92]. Correlations were found between structures and activities against murine P388DI and L1210 cells, human T-lymphocyte cell lines and, in some cases
- , mutagenous properties were also shown. Freccero et al. examined the photogeneration by laser flash photolysis and reactivity of naphthoquinone methides as well as their activity as purine selective DNA alkylating agents [93]. Farrell et al. studied the mechanism of the cytotoxic action of naphthoquinone
Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing
Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32
- cellular internalization in Vero cells. These data support that both 3-(N,N-dimethylamino)propyl and fma groups are required for optimal internalization in the three cell lines. Of special interest was the absence of cytotoxic effects in Vero cells at a 50 μM extracellular ON concentration for 72 h
Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting
Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29
- group (-CH2NH2) as a handle for conjugation to cytotoxic drugs (Figure 2, ligands 2 and 4) [28][29][30]. Conjugates of the functionalized ligands 2 and 4 with paclitaxel (PTX) via a 2’-carbamate with a self-immolative spacer and the lysosomally cleavable Val-Ala linker [31] were synthesized (Figure 2
- ) proved less potent than α-amanitin in all cell lines (see Table 3, cf. entry 1 with entries 2–4). In general, one can conclude that the “uncleavable” compounds 7 and 8 are much less cytotoxic than free α-amanitin, while the lysosomally cleavable compounds 9–11 show variable results, with RGD compound 9
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
- concentrations (1 µM and 5 µM) of these compounds. The data (treated cells and untreated controls) were plotted together to compare the results (Figure 2). Shibata reagents 1 and 2a were not very cytotoxic at 5 μM. Perfluorinated phenylthio reagent 2b and perfluorinated phenyl reagent 3a showed similar, but
- moderate (45.3%), but low at 1 μM (17.9%). The non-fluorinated diphenyl iodonium salt 3o, on the other hand, was weakly cytotoxic at both concentrations (1 μM, 7.5%; 5 μM, 10.1%). Analysis of the perfluorinated phenyl reagent 4a with a triisopropylphenyl ligand displayed strong cytotoxicity (93.7%) at 5 μM
Recent developments in the asymmetric Reformatsky-type reaction
Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21
- in the presence of LiI. A subsequently deprotection of this product by treatment with TFA led to the expected naturally occurring cytotoxic macrolide epothilone D. It must be noted that this novel highly convergent and stereocontrolled total synthesis of epothilone D clearly differed from other
- , cebulactam A1, and ansamacrolactams. In addition, novel total syntheses of prostaglandin E2, the cytotoxic agent epothilone D, and protein inhibitor ABT-737 along with formal syntheses of the protein inhibitor tedanolide C, the neprilysin inhibitor sacubitril, the antiproliferative agent jatrophane diterpene
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