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Search for "inhibitor" in Full Text gives 405 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

  • Rebeka Jójárt,
  • Szabolcs Pécsy,
  • György Keglevich,
  • Mihály Szécsi,
  • Réka Rigó,
  • Csilla Özvegy-Laczka,
  • Gábor Kecskeméti and
  • Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

Graphical Abstract
  • estrone derivatives, including estrone-3-sulfate could be blocked. Inhibitors based on the estrane core could have multiple inhibitory properties concerning the two enzymatic steps of the sulfatase pathway and OATP2B1-mediated membrane transport of estrone-sulfate. The inhibitor design is usually based on
  • -sulfate uptake by OATP2B1 [6]. None of the steroidal STS or 17β-HSD1 inhibitors reached the clinical trial, which is mainly due to their retained estrogenic activity. This side-effect could be eliminated by the inhibitor design based on the 13-epimer of natural estrone (13α-estrone, 13αE1OH) [17][18
  • of the steroid to the transporter protein. Additionally, inhibitory potencies of the newly-synthesized compounds on human placental STS and 17β-HSD1 have been tested in vitro (Table 3). None of the newly-synthesized derivatives proved to be a potent STS inhibitor, since the compounds suppressed the
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Published 14 Nov 2018

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

  • Jakob Bouton,
  • Kristof Van Hecke,
  • Reuven Rasooly and
  • Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

Graphical Abstract
  • ), an inhibitor of the RAP/TRAP (RNAIII-activating protein/target of RAP) quorum sensing system in S. aureus (Figure 1) [12][13][14]. Furthermore, hamamelitannin has been shown to inhibit biofilm formation and to potentiate the activity of antibiotics against staphylococcal biofilms in vitro and in vivo
  • optimal side chain substituents are an o-chlorobenzamide on the 5-position and a non-substituted benzamide on the 2’-position. In absence of any structural information of the inhibitor–target interaction, we were interested in replacing the core tetrahydrofuran scaffold by a pyrrolidine ring in order to
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Published 12 Nov 2018

Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid

  • Jacqueline Pollini,
  • Valentina Bragoni and
  • Lukas J. Gooßen

Beilstein J. Org. Chem. 2018, 14, 2737–2744, doi:10.3762/bjoc.14.252

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  • Jacqueline Pollini Valentina Bragoni Lukas J. Goossen Lehrstuhl für Organische Chemie I, Ruhr-Universität Bochum, ZEMOS, Universitätsstraße 150, 44801 Bochum, Germany 10.3762/bjoc.14.252 Abstract A convenient and sustainable three-step synthesis of the tyrosinase inhibitor 2-hydroxy-6
  • subsequent hydrogenation step. Overall, the target compound was obtained in an overall yield of 61% based on the unsaturated anacardic acid content and 34% based on the crude CNSL. Keywords: cashew nutshell liquid; cross-metathesis; renewable feedstock; sustainable chemistry; tyrosinase inhibitor
  • synthesis of the most potent tyrosinase inhibitor among them, the ginkgolic acid (13:0), starting from crude CNSL (Scheme 1, left). Tyrosinase is an enzyme [28] which is responsible for browning of fruits and vegetables as well as skin pigmentation [29]. Furthermore, it is linked to several
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Published 31 Oct 2018

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

  • Matthew J. Styles and
  • Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

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  • compounds, R8 displayed the greatest inhibitory activity in SdiA – inhibition to 120% with an IC50 of 44 μM. Interestingly, similar compounds with shorter tail lengths are potent inhibitors in other receptors: R6, with a 9-carbon tail, is a potent inhibitor of QscR and LasR, and Q9, with an 8-carbon tail
  • , is a potent inhibitor of QscR [64]. A set of other compounds containing aryl tails with large substituents (such as Br, I, and SCH3) also partially inhibit SdiA; specifically, thiolactone 16 (mBTL), which has a long (4 atom) linker between the amide and phenyl, inhibited SdiA activity by 89% with an
  • sub-micromolar IC50 (318 nM). Compound 11 was originally designed by the Meijler lab to react with a cysteine in the AHL-binding pocket of LasR, thereby acting as an irreversible inhibitor [44]. SdiA does have a cysteine in the binding pocket (Cys45, see Figure 1D), but it is positioned near carbons 3
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Published 17 Oct 2018

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

  • Christian Schütz and
  • Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

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  • intermediate between PqsD and anthraniloyl-CoA [54]. Upon simplification and rigidification through reduction in size as well as removal of rotatable bonds inhibitor 13 was obtained carrying the characteristic secondary alcohol of this class. Notably, both enantiomers of 13 show similar potency, but different
  • the substrate tunnel [57]. The binding models of the ureidothiophene and nitrophenylmethanol classes even allowed for the generation of a merged inhibitor [58]. One major liability of this class, however, was the general inefficacy in whole cell assays, which could not be improved, even through the
  • ]. Starting from a PqsR inhibitor, changes of the electronic properties on the benzimidazole by introducing an electron-donating group led to a higher PqsBC inhibitory activity, while decreasing the affinity to PqsR (compound 28). Nevertheless, it was shown that blockage of PqsBC leads to a reduction of HHQ
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Published 15 Oct 2018

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

  • Matthew B. Calvert,
  • Varsha R. Jumde and
  • Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

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  • of LecA with its electrophilic epoxide warhead [40]. It could be demonstrated that 11 is a covalent lectin inhibitor, which provided the first proof-of-concept for this new approach to lectin inhibition. To date, the most potent LecA inhibitor 12 has been designed by the Pieters group, where two
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Published 11 Oct 2018

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

  • Gergő Mótyán,
  • László Mérai,
  • Márton Attila Kiss,
  • Zsuzsanna Schelz,
  • Izabella Sinka,
  • István Zupkó and
  • Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

Graphical Abstract
  • hormones, and therefore, in the development of prostate cancer [1]. According to extensive structure–activity relationship and docking studies, a potent steroidal inhibitor should possess certain structural characteristics for efficient P45017α inhibition [1][2][3], such as (i) a five or six-membered non
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Published 08 Oct 2018

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

  • Nisachon Khunnawutmanotham,
  • Cherdchai Laongthipparos,
  • Patchreenart Saparpakorn,
  • Nitirat Chimnoi and
  • Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

Graphical Abstract
  • potent activities with inhibitory concentration (IC50) values in the nanomolar concentration range. Among them, the 2,3-difluorobenzylpyridinium-containing compound was the most potent inhibitor with an IC50 value of 1.53 ± 0.01 nM. Docking studies revealed that the synthesized compounds inhibit the
  • target enzyme by a dual binding site mechanism whereby the coumarin portion binds with the peripheral anionic site while the N-benzylpyridinium residue binds with the catalytic anionic site of the enzyme. Keywords: acetylcholinesterase inhibitor; 3-aminocoumarin; N-benzylpyridinium; dual binding site
  • inhibitor; synthesis; Introduction An increasing number of countries are facing a rapid growth of the elderly population. The birth rates of many countries, such as China, Japan, and Thailand are lower than the number theoretically required for the replacement of successive generations, resulting in an
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Published 02 Oct 2018

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

  • Eszter Lajkó,
  • Sarah Spring,
  • Rózsa Hegedüs,
  • Beáta Biri-Kovács,
  • Sven Ingebrandt,
  • Gábor Mező and
  • László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

Graphical Abstract
  • =Aoa) could be attributed to the presence of butyrate, which has been demonstrated to inhibit the proliferation as well as to induce apoptosis and cell cycle arrest in different cell lines (e.g., colon carcinoma, melanoma, T-cell lymphoma) as a histone deacetylase inhibitor and/or via activation of
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Published 26 Sep 2018

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

  • Maroš Bella,
  • Sergej Šesták,
  • Ján Moncoľ,
  • Miroslav Koóš and
  • Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

Graphical Abstract
  • swainsonine, interferes with the glycosylation pathway where it specifically inhibits GH38 glycoside hydrolases [23][24]. Up to date, swainsonine is the most potent Golgi mannosidase II (GMII) inhibitor. It is known that inhibition of the biosynthesis of complex N-glycans in the Golgi apparatus influences
  • structure and related pyrrolidines are of particular interest as potential candidates for cancer treatment [26][27]. Our research interest has been focused on searching for efficient inhibitors of α-mannosidases from the GH38 family. Another important feature required for such a potential inhibitor is its
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Published 17 Aug 2018

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

  • Jiyun Sun,
  • Xiaohua Zhen,
  • Huaibin Ge,
  • Guangtao Zhang,
  • Xuechan An and
  • Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

Graphical Abstract
  • agents [7][8][9][10][11][12][13][14][15][16]. For example, fluoxetine hydrochloride (Figure 1, A) [4][9][10] (Prozac®, an antidepressant and a selective serotonin reuptake inhibitor for the treatment of major depressive disorders, obsessive–compulsive disorders, etc.), teriflunomide (Figure 1, B) [11][12
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Published 15 Jun 2018

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

  • Veronika Hladíková,
  • Jiří Váňa and
  • Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

Graphical Abstract
  • -oxohexanoic acid with 4-fluoro-3-(4-methylphenyl)sydnone (Scheme 12). Unfortunately the regioselectivity of the reaction was not specified. An aryne generation (Scheme 13) was also used for the synthesis of a key intermediate of the potent antitumor PARP inhibitor – niraparib – containing an indazole core
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Published 05 Jun 2018

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

  • Gernot A. Eller,
  • Gytė Vilkauskaitė,
  • Algirdas Šačkus,
  • Vytas Martynaitis,
  • Ashenafi Damtew Mamuye,
  • Vittorio Pace and
  • Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

Graphical Abstract
  • , therein several drug molecules, agrochemicals, dyestuffs, compounds for optoelectronic purposes, complexing ligands and more contain a pyrazole nucleus [1][2][3][4][5][6][7][8]. Condensed pyrazoles are of special interest, as a commonly used example the phosphodiesterase 5 (PDE5) inhibitor sildenafil
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Published 04 Jun 2018

Novel unit B cryptophycin analogues as payloads for targeted therapy

  • Eduard Figueras,
  • Adina Borbély,
  • Mohamed Ismail,
  • Marcel Frese and
  • Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

Graphical Abstract
  • the other derivatives 23 and 24 (Figure 4). Besides hydrogen bond formation and binding affinity of inhibitors 2, 23 and 24, π-interactions and hydrophobic contacts with the binding pocket of the vinca domain were detected that would in turn increase the affinity of the inhibitor and its effect on the
  • magenta. Docking of 22 to the vinca domain of β-tubulin. Surface and backbone of β-tubulin are shown in blue, GDP in yellow. No hydrogen bond formation was detected. The orientation of the azidoethoxy-ethoxyethyl substituent prevents the inhibitor from the correct interaction with the protein. The epoxide
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Published 01 Jun 2018

One hundred years of benzotropone chemistry

  • Arif Dastan,
  • Haydar Kilic and
  • Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Graphical Abstract
  • and in a number of other natural compounds that have shown a highly diverse range of biological activity [1][2][3][4][5][6][7][8][9], like the inhibitory activity of inositol monophosphatase [10][11], antitumor [12], antibiotic [12][13], and antibacterial activity [14] and lipoxygenase inhibitor
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Published 23 May 2018

An overview of recent advances in duplex DNA recognition by small molecules

  • Sayantan Bhaduri,
  • Nihar Ranjan and
  • Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Graphical Abstract
  • . In addition, they act as potent topoisomerase II inhibitor at the concentration 10 μM and show antiproliferative and cytotoxic activities in breast cancer cell line in the range of 81.70 μM and 200.00 μM. Conjugate 41 with a 6-aminophenyl moiety appeared to be the most effective among others
  • observed that the conjugates with alkynyl side chains show excellent E. coli DNA topoisomerase I inhibition properties with IC50 values of <5.0 μM, which was attributed to critical interactions between the inhibitor side chain and amino acids of the active site of DNA topoisomerase I, as suggested by the
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Published 16 May 2018

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

  • Fabiana Pandolfi,
  • Isabella Chiarotto and
  • Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

Graphical Abstract
  • reaction under milder conditions. 2-Ethynylnaphthalene (2a) is a small molecule with a high and selective biological activity. In particular, this molecule has been demonstrated to be a selective inactivator of cytochrome P-450 2B4 [26] and an inhibitor also of other cytochrome P-450 isoforms [27]. We thus
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Published 23 Apr 2018

An efficient and facile access to highly functionalized pyrrole derivatives

  • Meng Gao,
  • Wenting Zhao,
  • Hongyi Zhao,
  • Ziyun Lin,
  • Dongfeng Zhang and
  • Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

Graphical Abstract
  • in medicinal chemistry (Figure 1), such as analgesic agent 1 [1], BET bromodomain inhibitor 2 [2], selective PARP-1 inhibitor 3 [3], histone deacetylase inhibitor with antitumor activity 4 [4], Flavivirus inhibitor 5 [5], and for treating cardiovascular diseases (atorvastatin, 6) [6]. A number of
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Published 20 Apr 2018

Phosphodiester models for cleavage of nucleic acids

  • Satu Mikkola,
  • Tuomas Lönnberg and
  • Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

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Published 10 Apr 2018

Enzyme-free genetic copying of DNA and RNA sequences

  • Marilyne Sosson and
  • Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

Graphical Abstract
  • extension. The hydrolyzed, free nucleotide can still bind to the extension site on the template, and in doing so, prevent the activated form from entering the site, acting as a competitive inhibitor [32]. So, both the rate of hydrolysis and the strength of the inhibitory effect were important factors to be
  • now a pseudo-first order reaction [33][34]. To properly model the inhibition, both the rate of hydrolysis (kh) and the dissociation constant of the inhibitor–primer/template complex have to be known. The latter (Kdh) is often similar to the Kd value for the complex with the activated monomer, so that
  • the dissociation constant (Kd). It takes into account the rate of hydrolysis with the corresponding rate constant (kh), the binding equilibrium for the hydrolyzed monomer that acts as inhibitor (Kdh), and it assumes a single rate-limiting chemical step (kcov); B, B' = nucleobase = OH for RNA. Binding
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Published 12 Mar 2018

Carbohydrate inhibitors of cholera toxin

  • Vajinder Kumar and
  • W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

Graphical Abstract
  • lactose-2-aminothiazoline conjugate as a CT antagonist. Its affinity for CTB was determined by monitoring the change in fluorescence of tryptophan-88, located in the GM1 binding site, upon titration of the protein with the inhibitor. Compound 6 showed excellent binding with a Kd value of 23 µM [41
  • , these compounds, 7 and 8, did not display good inhibition, the non-glycosylated ligands offered new avenues for better CT ligand designs. Multivalent receptor-binding inhibitors The five-fold symmetry of AB5 toxins provides a strong encouragement to think about multivalent inhibitor design from (even
  • weakly binding) monovalent inhibitors [30][31]. Multivalent ligands have been long applied to a wide range of protein targets [43][44][45]. By having an inhibitor that may bind simultaneously with multiple binding sites, the dissociation rate of the complex is effectively reduced. Even if any individual
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Published 21 Feb 2018

Synthesis of fluoro-functionalized diaryl-λ3-iodonium salts and their cytotoxicity against human lymphoma U937 cells

  • Prajwalita Das,
  • Etsuko Tokunaga,
  • Hidehiko Akiyama,
  • Hiroki Doi,
  • Norimichi Saito and
  • Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

Graphical Abstract
  • ]. Utilizing these reagents, we have successfully synthesized a wide variety of bioactive organofluorine compounds [24][25][26][27][28][29][30] including fluorinated thalidomide (antitumor) [24], fluorinated donepezil (cholinesterase inhibitor) [25], and fluorinated camptothecin (anticancer) [26]. During our
  • only fragmented reports on the biological activity of diaryliodonium salts [44][45][46][47][48][49]. Goldstein et al. [45] and Doroshow et al. [46] reported that some diaryliodonium salts show effective antimicrobial and NOX inhibitor activity, respectively. Several aryliodonium salts, aryliodonium
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Published 07 Feb 2018

Recent developments in the asymmetric Reformatsky-type reaction

  • Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

Graphical Abstract
  • to prepare these products. For example, this methodology was employed in 2014 by Kawanishi and Yamakoshi to develop the first total synthesis of naturally occurring prunustatin A, a novel inhibitor of glucose-regulated protein 78 expression [17]. As shown in Scheme 2, the key step of the synthesis
  • the C1–C11 fragment of naturally occurring protein inhibitor tedanolide C. Intermolecular aza-Reformatsky reactions The diastereoselective zinc-mediated aza-Reformatsky reaction represents a powerful and direct methodology to prepare chiral β-aminoesters [25], which represent key intermediates in
  • /cholecyctokinin-B receptor antagonist AG-041R starting from Reformatsky chiral product 33a. Earlier in 2015, Ley et al. reported an efficient synthesis of a precursor of the neprilysin inhibitor sacubitril based on a zinc-mediated aza-Reformatsky-type reaction [31]. Indeed, this convergent synthesis featured a
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Published 02 Feb 2018

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

  • Thanh-Tuân Bui,
  • Fabrice Goubard,
  • Malika Ibrahim-Ouali,
  • Didier Gigmes and
  • Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

Graphical Abstract
  • applications of phenoxathiin dioxide ranged from antimicrobial activity [67] to the use as inhibitor for Hepatitis C virus infection [68]. Here, in the context of OLEDs, Lee et al. reported two blue TADF emitters, P1 and P2 (see Figure 10), containing a phenoxaphosphine oxide or a phenoxathiin dioxide acceptor
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Published 30 Jan 2018

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

  • Ranjana Aggarwal and
  • Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

Graphical Abstract
  • derivatives were evaluated for their CHK1 kinase inhibitory activity. Pyrazolo[1,5-a]pyrimidine derivative 142 with R1 = 3-(1-methylpyrazolyl), R2 = H, R = 3-pyridyl and R´ = 5-(3-methylthiazolyl) was found to be the most potent, selective CHK1 inhibitor. Azeredo et al. [98] reported a similar synthesis of 7
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Published 25 Jan 2018
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