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Search for "in vivo" in Full Text gives 292 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins
Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68
- . The CsCCD2(S323A) mutant could also catalyze the conversion of β-carotene (6) to 1 [91]. BdCCD4.1 and BdCCD4.3, the homologs of CsCCD2 from B. davidii, were discovered by bioinformatic analysis. In vitro and in vivo experiments demonstrated that these two enzymes could cleave zeaxanthin (7), but the
- clearance in vivo. Only a few plants can produce crocins, and the content of crocins in these plants is very low. Due to the numerous chiral centers, the total synthesis of crocins is challenging. Therefore, heterologous biosynthesis of crocins utilizing the synthetic biology strategy holds great potential
Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization
Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66
- contrast to Kang’s chemical synthesis route, this biotransformation provided a more efficient and productive strategy for the desoaminylation of macrolide aglycones. Combining in vitro and in vivo enzymatic reactions together, this chemoenzymatic platform exhibits the potential to access a broader range of
- macrolactonization, leading to the formation of tylactone (39) in 69% yield. Furthermore, the Streptomyces strain S. venezuelae DHS316 [76] performed an in vivo glycosylation resulting in M-4365 G1 (50) in 15 linear steps and 4.6% overall yield from commercial resources. With regio- and stereoselective C–H
- clinical trials for the treatment of non-small-cell lung cancer and platinum-resistant ovarian cancer, but was halted in phase II due to dose-limiting peripheral neuropathy and limited efficacy in vivo [80]. However, this family of depsipeptides remains of therapeutic significance and has recently been
A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A
Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51
- aminocyclitol moieties. The biosynthesis of the aminocyclitol has been proposed to proceed through six enzymatic steps from glucose 6-phosphate through myo-inositol to the final methylenedioxy-containing aminocyclitol. Although there is some in vivo evidence for this proposed pathway, biochemical support for
- essential for in vivo antimicrobial activity suggesting a distinct biological function independent of ribosome binding. The hygromycin A biosynthetic gene cluster has been identified and the biosynthesis of the aminocyclitol has been proposed (Figure 1) [8][9]. Starting from glucose-6-phosphate, the pathway
- annotations and in vivo studies [8]. However, validation by in vitro approaches or biochemical analysis of the individual enzymes is lacking. Here, we verify that Hyg17 is a myo-inositol dehydrogenase and show that it has a distinct substrate scope. In addition, we use sequence similarity networks to compare
Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors
Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46
- (i.e., 13b) and 3.17 (i.e., 13c). We were thus curious to see how the structural change from a heteroaromatic thiazole unit to a partially saturated thiazoline moiety affected the in vitro and in vivo efficacy of the target compounds. All compounds that were prepared to explore the SAR of substituted
- 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, i.e., 13a–c, and 7a–c, the acylated analogues 14a–c and 16a–f, as well as selected aminoboranes 17d and 17e, were tested for target affinity in dedicated in vitro tests, as well as for herbicidal effects in vivo upon preemergence application to plants. Based
- from LEMPA could be observed for all three target compounds 7a–c (pI50 5.9–6.3, Table 2, entries 1–3). However, this was paired with strong in vivo efficacy on the level of internal standard 5 and exceeding the results obtained for cinmethylin (1) and methiozolin (2). Whilst compounds 7a–c afforded
Switchable molecular tweezers: design and applications
Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45
- release of siRNA or miRNA encapsulated within them into the solution in vitro and in vivo [21]. The closed conformation of 2 with parallel alkyl chains acts as a building block of the bilayer membrane and is packed together with other lipids. When the surrounding medium becomes acidic, the tweezers adopt
Synthesis of ether lipids: natural compounds and analogues
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
- with the development of edelfosine (an anticancer drug). More recently, ohmline, a glyco glycero ether lipid that modulates selectively SK3 ion channels and reduces in vivo the occurrence of bone metastases, and other glyco glycero ether also identified as GAEL (glycosylated antitumor ether lipids
- generally more abundant in cancer tissues than in normal human tissues [14]. It was also reported that the rate of neutral ether lipids in cancer cell line (quantified in vitro) was correlated to the tumorigenicity of the cancer cell lines in vivo [15]. However, the improvement of the analytical technics
- of glycerol is readily hydrolyzed in vivo and in serum [100][101]. With the aim to produce more stable compounds, the modification of the sn-2 position of the glycerol was reported. A first option consisted in placing a carbamate function leading to the synthesis of methyl carbamoyl-PAF (1-O
Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO2F2)
Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68
- interaction between the drug candidate and the target protein, to further improve the efficacy of the potential drug [9]. The nitrile group can also function as a metabolic blocking site to inhibit the oxidative metabolism of molecules to improve metabolic stability in vivo [10]. Consequently, the development
Asymmetric synthesis of a stereopentade fragment toward latrunculins
Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32
- synthesize latrunculin analogues for chemical biology studies. In particular, our initial goal was to protect an inactive lactol-opened form of latrunculins, which could cyclize in vivo upon deprotection under a specific stimulus (light or enzyme, for instance) for biological applications. This challenge
Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements
Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26
- enzyme-catalyzed reactions and to gain insight into the operation and modeling of metabolic pathways [3] and genome wide networks [4], particularly if one has limited in vivo measurements of the substances in the pathway [5][6]. However, we have observed that a fair number of investigators overlooked
Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series
Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23
Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors
Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14
- , and furthermore in vivo antitumoral and antimetastatic efficacy in early and late-stage colon cancer models and biodistribution after single dose oral administration. This study was carried out to further elucidate oral camptothecin (CPT)-loaded amphiphilic cyclodextrin nanoparticles for the local
- treatment of colorectal tumors in terms of their drug release behavior and efficacy in 3-dimensional tumor models to predict the in vivo efficacy of different nanocarriers. The main objective was to build a bridge between formulation development and in vitro phase and animal studies. In this context, CPT
- delivery system, developed in our previous research for the treatment of CRC to build a bridge between in vitro characterization and in vivo animal efficacy studies and to establish a screening tool for nanoparticulate formulations for poorly bioavailable anticancer drugs administered through a non
Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements
Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184
- -CD. It is notable that these measured solubilities are also superior to those of the commercially utilized formulations containing ethinylestradiol and micronized progesterone. Further investigation should include in vivo experimentation to assess the efficacy of the four CD inclusion complexes as
New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling
Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161
- financial support from Brazilian Agencies CNPq and CAPES. The authors are also grateful to the Graduate Programme in Pharmaceutical Sciences (PPGCF/UFRGS) according to these: Obtenção De Derivados Triterpenos Semissintéticos Com Atividade Antitumoral E Antiviral In Vitro E In Vivo. PhD Thesis 2016
On drug discovery against infectious diseases and academic medicinal chemistry contributions
Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141
- , parallel/combinatorial synthesis, multicomponent chemistry, metal-catalyzed coupling reactions as well as NMR, preparative/analytical liquid chromatography and mass spectrometry). – An improved understanding of molecular pharmacology along with in vitro or in vivo assays to detect various aspects of drug
- second original class of bacterial gyrases inhibitors. In 2004, the nitro-bearing derivative 11, resulting from a high-throughput phenotypic-based screening, was patented by Pharmacia/Pfizer for its antibacterial properties [122][123]. Even if this compound was also effective in vivo, many synthesis and
- evaluation iterations were undertaken at Astra Zeneca to reach, in 2014, zoliflodacin (12) [124] which is currently undergoing a phase 3 clinical trial, sponsored by Entasis Therapeutics [125]. Interestingly, further synthetic work is going on [126][127], including on original analogues active in vivo
Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions
Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134
- (phosphoenolpyruvate as phosphate donor) is strongly favouring ATP synthesis both in vivo and in vitro, this reaction was originally considered to be irreversible in cells and a point of flux control. Newer findings showed the reaction to be actually an equilibrium, although positioned far on the product side [27][28
A Streptomyces P450 enzyme dimerizes isoflavones from plants
Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113
- CYP158C1 is the most likely enzyme for isoflavone dimerization. Interestingly, different from the in vivo extract, in vitro experiments gave a major dimer 5, a 3’,3’ coupled dimer assigned by MS–MS (Figures S8 and S14, Supporting Information File 1). Although dimer 3 was not visible in the HPLC analysis, a
- trace amount of 3 was detected by HRMS analysis (Figure S8, Supporting Information File 1). Redox partners might be responsible for the different regioselectivity between in vivo and in vitro reactions, as it has been reported that different reductases would lead to different diastereomeric dimers of
New azodyrecins identified by a genome mining-directed reactivity-based screening
Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102
- during the isolation process, trans-azodyrecins were detected in the fresh extracts of the solid cultures from both strains, suggesting that they are also generated in vivo (Figure S2 in Supporting Information File 1). The NMR spectra of compound 7 are similar but distinct from those of the known
Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli
Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89
- overexpression in E. coli [19]. Isopentenyl diphosphate isomerase (IDI) from E. coli, which balances IPP and DMAPP in vivo, was also included in our construct. To initially test the efficiency of this two-step artificial pathway, we constructed strains DL10001 (phoN, ipk and idi plus the lycopene-producing genes
Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity
Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72
- residue was dissolved in methanol (100 µL), and analyzed by HRMS/MS. Denaturation of proteins was performed at 95 °C for 10 min (negative control). Additionally, E. coli BL21 derived enriched membrane fractions served as negative control. In vivo assays: In vivo assays (100 mL) were performed using E
- performed in a 75 L X-Cube Bioreactor (Braun Biotech International) using 30 L of Terrific Broth medium (Carl Roth GmbH) enriched with 4 mL/L glycerol and 60 mg/L kanamycin. Similar to the in vivo culture assays, the culture was cooled to 16 °C at an OD600 of 1 and heterologous production induced with IPTG
Menadione: a platform and a target to valuable compounds synthesis
Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43
- epoxides are formed through oxidation reactions in vivo, that occur in protein processes dependent on vitamin K [96][97]. Dwyer and co-workers described a procedure using sugar-derived hydroperoxides for the synthesis of epoxides in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as base [98][99
Synthesis and late stage modifications of Cyl derivatives
Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19
- naturally occurring HDAC inhibitors contain sulfur moieties like, e.g., disulfides or thioesters. They seem to lack a zinc-chelating group at first sight, but the disulfide or thioester acts as a prodrug and are reduced/cleaved in vivo to liberate the free thiol, a strong Zn-binding group [24][25]. Results
1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis
Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5
- in vitro and in vivo against Leishmania donovani, which causes visceral and cutaneous leishmaniasis. It has been observed that the prodrugs improved efficacy when compared to buparvaquone. Parvaquone (14) is a naphthoquinone with antitheilerial properties that is commercialized for the treatment of
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
- counterparts during DNA or RNA synthesis, a biological role that is crucial for cellular reproduction [2]. Most of the drugs that are incorporated in the viral DNA upon phosphorylation in vivo block the DNA polymerase enzyme. However, DNA polymerase recognizes 2’,3’-dideoxynucleosides as substrates, which are
- as zidovudine, didanosine, zalcitabine, stavudine, lamivudine (1), and abacavir (a carbanucleoside) for treating HIV infection, along with protease and nonnucleoside reverse transcriptase inhibitors (NNRTIs). Phosphorylation of 1,3-oxathiolane nucleosides, such as 3TC (1) and FTC (2), occurs in vivo
- enantiomer in a chiral environment [32]. Additionally, on the grounds that living systems are, in a sense, themselves chiral, each of the enantiomers of a chiral drug can perform very differently in vivo. Therefore, there is a requirement to synthesize enantiomerically pure nucleosides that are free from
Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing
Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171
- millimetre-sized defects (common in most in vivo tissue-engineering work in small animal models) [64]. Kim and co-workers reported a method in 2009, whereby a 3D-plotting system was coupled to a cryogenic refrigeration system [65][66]. Using these systems 3D scaffolds were prepared by printing collagen
- ]. They report 3D-printed structures which could be used for minimally invasive cell delivery (see Figure 3). Moreover, hierarchical structures with varying local pore sizes were obtained by tuning the substrate temperature during printing, which led to control over vascularisation density in vivo. Biçen
- does not leak out of the needle bore after being applied. The GelMA can then be implied with minimal intrusion to the patient which decrease the chance of trauma to the patient. Koshy et al. also report that in vitro and in vivo testing showed that cryogelated GelMA is cell and tissue compatible
Strategies for the synthesis of brevipolides
Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157
- of 14.0 μM observed for brevipolide I (9) (Table 1 entry 9) [1][12]. Moving forward, cytotoxicity examination against MCF-7 human breast carcinoma cells was done for all the brevipolide members (Table 1, entries 1–15) [1][4][12]. Brevipolides A–H (1–8) were evaluated in vivo (Table 1, entries 1–8
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