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Search for "inhibitors" in Full Text gives 474 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors
Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108
- ]. Specifically, bisphosphonates act as osteoclast resorption inhibitors, augmenting the bone density and preventing osteoporosis [4]. Moreover, some bisphosphonates have gained attention as potential antiinflammatory agents by in vitro and in vivo assays [5][6][7][8]. Additionally, bisphosphonates have been
- molecular docking studies were performed to account for a possible action mechanism as MMP-8 and MMP-9 inhibitors. Results and Discussion Chemistry As part of our ongoing interest in the discovery of new antiinflammatory agents, our research group have previously addressed the synthesis and in vivo
- mechanism of action of the bisphosphonates 3–6, we propose that the tested derivatives are acting as MMP inhibitors. In this respect, MMP-8 and MMP-9 isoenzymes are related to inflammatory processes in different tissues [32][33][34][35]. Furthermore, for MMP-8 and MMP-9, enzyme–inhibitor interaction modes
Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions
Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106
- crispine A isolated from Carduus crispus L has antitumor activity [3]. Erythrina alkaloids have curare-like neuromuscular blocking activities [4], and also antioxidant activity against DPPH free radicals [5]. Lamellarins isolated from marine invertebrates [6] are inhibitors for HIV-1 integrase and also
Anthelmintic drug discovery: target identification, screening methods and the role of open science
Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105
- developed helminth analysis methods using CellProfiler. A virtual screening approach was used to identify inhibitors of S. mansoni thioredoxin glutathione reductase [140]. These virtual hits were then tested in a CellProfiler-based high content screen using S. mansoni schistosomula, which determines both
Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore
Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98
- in the last few years due to the discovery that truxillic acid derivatives are inhibitors of FABP (fatty acid binding proteins), which are responsible for the cellular reuptake of anandamide, an endocannabinoid neurotransmitter, and that they can be involved in a very efficient treatment for chronic
A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes
Beilstein J. Org. Chem. 2020, 16, 1092–1099, doi:10.3762/bjoc.16.96
- the HRMS measurements is appreciated. Funding The University of Zagreb short term scientific support under the title “Synthesis and functionalization of novel (hetero)polycyclic photoproducts as cholinesterase inhibitors” is gratefully acknowledged.
Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones
Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95
- active small molecules that exhibit antihypertensive activity [7][8]. Moreover, these heterocycles can be used as 5-HT3 antagonists [9], rho kinase inhibitors [10], thymidylate synthetase inhibitors [11], PARP-1 inhibitors [12], melatonin MT1 and MT2 receptor agonist [13], and fascin-targeted
Fluorinated phenylalanines: synthesis and pharmaceutical applications
Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91
- over the last few decades. ᴅ- or ʟ-fluorinated phenylalanines have had considerable industrial and pharmaceutical applications and they have been expanded also to play an important role as potential enzyme inhibitors as well as therapeutic agents and topography imaging of tumor ecosystems using PET
- , geometry, conformation, reactivity, and moreover the bioavailability of the analogue [1]. Fluorinated amino acids (FAAs) have considerable industrial and pharmaceutical potential [2]. Also, they have played an important role as enzyme inhibitors as well as therapeutic agents [3][4]. Moreover, they modulate
- ees < 98%. The products were hydrolyzed and deprotected in a two-step protocol to afford the desired products 77a,b [55] (Scheme 18). Interestingly substitution of Phe by either 77b or 77a in the proteasome inhibitors bortezomib or epoxymicin, led to an increase in the efficiency as anticancer
Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition
Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59
- inhibitors (HDACis). The targets of interest (TOI) are analogues of panobinostat, one of the most potent and versatile HDACi reported. By simply replacing the phenyl core of panobinostat with that of a diazine derivative, docking studies against HDAC2 and HDAC8 revealed that the four analogues exhibit
- lay the foundation for future design strategies toward more potent HDACis for HDAC8 isozymes and further therapeutic applications for neuroblastoma. Keywords: diazine; histone deacetylase; inhibitors; isozymes; panobinostat; Introduction One of the most important posttranslational modifications
- development of novel HDAC inhibitors (HDACis) has become a rapidly evolving area where targeted inhibition has emerged in clinical research as a potential therapeutic approach for the treatment of various cancers as well as neurodegenerative disorders and immune related diseases [3][4][5]. Of specific
Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin
Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46
- molybdopterin [1]. Owing to this biological relevance, pterins are an attractive building block in the development of various pharmaceuticals, with methotrexate being the most well-known [2]. In addition to pteridine derivatives being used as inhibitors of dihydrofolate reductase and dihydropteroate synthase
- , pterins have been a useful scaffold in the development of inhibitors of ricin [3][4], methionine synthase [5], nitric oxide synthase [6], shigella [7], and aldose reductase [8], as well as for treatment of leishmaniosis [9]. In addition to their therapeutic potential, pterin derivatives have been an
- for ricin toxin A (RTA) inhibitors [14]. By deprotonation of the lactam NH, and conversion to the DBU salt, the pterin easily dissolves in methanol at high concentrations, unprecedented for unfunctionalized pterins. This greatly accelerated the development of a library of bioactive pterins, as it
Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt
Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41
- nucleoside analogues which can either act as antimetabolites or as nucleoside reverse transcriptase inhibitors (NRTIs). Two of the most common 5-fluoropyrimidines are the cytostatic 5-fluorouracil (1) [27] and the antimycotic prodrug 5-fluorocytosine (2) [28][29], which is also part of the anti-HIV agents
Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors
Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25
- dioxygenase (HPPD) inhibitors. Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD (AtHPPD) inhibitors, in particular compounds I12 (Ki = 0.011 µM) and I23 (Ki = 0.012 µM), which exhibit similar activities to that of mesotrione, a commercial HPPD herbicide (Ki
- various species and genera and providing a theoretical basis for the design of inhibitors that are highly selective and safe [2]. In plants, HPPD inhibitors competitively restrain HPPA from chelating to FeII. The production of plastoquinone is inhibited and phytoene is accumulated when the transformation
- of HPPA to HGA is interfered with an HPPD inhibitor [9][10]; consequently, plants become severely damage when exposed to sunlight, ultimately resulting in bleaching symptoms followed by necrosis and death [11][12]. Therefore, HPPD inhibitors play important roles in the herbicide industry. In addition
Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo
Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14
- hemithioindigo-based indanone-like tubulin inhibitors (HITubs) and optimised their cellular potency as antimitotic photopharmaceuticals. These HITubs feature reliable and robust visible-light photoswitching and high fatigue resistance. The use of the hemithioindigo scaffold also permitted us to employ a para
- understanding MT biology; and optogenetic modifications of tubulin have never succeeded. Instead, studies of the roles of MTs in these processes overwhelmingly rely on small molecule tubulin inhibitors [1]. Due to the non-invasiveness and high spatiotemporal precision with which optical stimulation can be
- development beyond classical small molecule inhibitors; since the spatiotemporal complexity inherent to the diversity of tubulin-dependent cellular processes may finally yield to studies that can leverage high-spatiotemporal-specificity optical control to deliver cell-specific, time-reversible modulation of
Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction
Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3
- composed of both, an imidazo[1,2-a]pyridine ring and the phosphoryl group. The combination of these functional groups can be found in bisphosphonates and phosphonocarboxylates [8][9][10] – inhibitors of the therapeutically important enzymes, farnesyl pyrophosphate synthase (FPPS) and Rab geranylgeranyl
- transferase (RGGT), respectively. Results and Discussion We have previously synthesized a number of phosphonocarboxylates (PC) to study their structure–activity relationship with RGGT, using compounds 1 and 2 as advanced intermediates in the synthesis of RGGT inhibitors (Figure 1) [10][11]. We have found that
Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose
Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2
- cationic antimicrobial peptides with the negatively charged phosphate and carboxylate groups in LPS domains. Suitable inhibitors intercepting the attachment of Ara4N units to the lipid A and inner core region might restore sensitivity towards the cationic antimicrobial drugs as a novel approach to combat
- the looming antibiotic crisis [5]. 4-Amino-4-deoxy-ʟ-arabinose units are activated as the phosphodiester-linked undecaprenyl derivative [6], which is then transferred by the action of several Ara4N transferases (ArnT, Figure 1) [7]. The synthesis of potential inhibitors of the biosynthesis of Ara4N
- have frequently been exploited as potential inhibitors for glycosyl transferases since the carbon–phosphorus bond is not hydrolyzed in the active site of glycosyl transferases [10][11][12][13]. Herein, we report on the synthesis of α-anomeric C-arabinosyl methylphosphonate ester derivatives as model
SnCl4-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives
Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295
- synthetic applications of 2,7-anhydro-Neu5Ac are available in the literature. Previously, we successfully constructed the fucosyl α(1→4) to Neu5Ac linkage of ganglioside HPG-7 using 2,7-anhydro-Neu5Ac derivatives as acceptors [6]. For utilization as selective sialidase inhibitors, Chen’s and Juge’s groups
- in the synthesis of inhibitors for N-acetylneuraminidases from different sources [42]. The ring opening of 5 was not trivial since the substrate had a sterically hindered quaternary anomeric center, unlike the tertiary anomeric center C-1 of 1,6-anhydro sugars [29][30][31][32][33][43]. Furthermore
Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica
Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293
- in combination with biofilm inhibitors [7]. Since finding an effective strategy to control biofilm formation remains a challenge, the effort to search for an effective antibiofilm agent was herein made. Invertebrate-pathogenic fungi, in particular the spider-pathogenic fungi, have recently proved to
- be a promising source of bioactive compounds [8][9][10]. Thus, during the current study, which is part of a project aiming to discover novel biofilm inhibitors from Thai fungi [11], a number of invertebrate-pathogenic fungi collected from various parts of Thailand were studied for production of
- . Conclusively, even though the mode of action of the pigmentosins remains to be studied, they constitute promising candidates for combination therapy with existing or novel antibiotics. So far, beauverolides have been found to be potent calmodulin (CaM) inhibitors [33], antiatherosclerotic agents [34], acyl-CoA
Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis
Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286
- identified. In addition, the development of new β-lactamase inhibitors is ongoing and may restore the activity of known β-lactams against β-lactamase-producing strains [2]. Unfortunately, most of these antibiotics rely on known modes of action and do not target novel binding sites. To circumvent established
One-pot synthesis of substituted pyrrolo[3,4-b]pyridine-4,5-diones based on the reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamide with amines
Beilstein J. Org. Chem. 2019, 15, 2840–2846, doi:10.3762/bjoc.15.277
- tested as dipeptidyl peptidase-4 (DPP4) inhibitors [4][5][6][7]. From the obtained results, the authors suggested these compounds as effective therapeutic agents for the treatment of diabetes mellitus. Further, it was shown that several synthetic molecules with a pyrrolo[3,4-b]pyridin-5-one core display
Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles
Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276
- first time, a study related to the activity of the products as nucleotide pyrophosphatase inhibitors. In this context, we also studied the biological activity of previously synthesized diindolofurans and the results are compared with those of benzofuroindoles. Results and Discussion Following a
- changes of the substitution pattern allow for a modification of the selectivity and activity of these compounds to these enzymes. Docking studies of h-ENPP1 inhibitors Molecular docking of the most potent compounds 5c and 6a (for ENPP1) and for 6e (exhibiting dual inhibition for both isozymes) were
- -shaped and π–alkyl related bindings were noticed, connecting Ile235, Phe220, Ala546, Trp322 and Ile419. The fluorine atom was perceived interacting with Ile419. Docking studies of h-ENPP3 inhibitors The binding of ENPP3 was studied for selective inhibitor 5e. A dual affinity was observed for 5h and 6e
Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission
Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274
- into the corresponding cis configuration [1]. The reverse reaction can be initiated with a different wavelength. In a biological context, this photochromism was exploited first by Erlanger and colleagues for enzyme inhibitors in 1968 [2], and ion channels in 1971 [3]. Their ingenious approach was
Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation
Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269
- promising activity shown by the compounds containing a thiazolidinedione nucleus cover numerous categories such as antihyperglycaemics [5], aldose reductase inhibitors (ARI) [6][7], anti-inflammatory [8][9], anti-arthritics [10], anticancer [11][12][13] and antimicrobial [14][15][16][17][18], etc., has made
In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines
Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231
- biological properties. They have been reported to have anticancer [1], antimicrobial [2][3] and antioxidant [3] activities and to act as inhibitors of hepatitis B virus [4]. The dihydro derivatives of tetrazolo[1,5-a]pyrimidines belong to a bit special kind of dihydropyrimidines due to the strong electron
Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors
Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214
- bioactivity, allows the probing of pharmacologically relevant systems with spatiotemporal resolution. A hetero-stilbene lead resulting from the screening of a compound that was originally designed as kinase inhibitor served as a starting point for the design of photoswitchable sirtuin inhibitors. Because the
- inhibitors has already been fruitful in the past [32][33]. Therefore, a focused kinase inhibitor library from GlaxoSmithKline was screened for biological activity on human sirtuin isoforms Sirt1–Sirt3. Aza-stilbene derivative GW435821X (2a, Figure 1), initially published as c-RAF kinase inhibitor, was
- identified as a moderately active Sirt2 inhibitor with low selectivity [34][35]. In this work, the photoresponsiveness of the hetero-stilbene core structure is examined. Furthermore, an intramolecular azologization approach is performed in order to obtain photoswitchable sirtuin inhibitors, which could be
Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica
Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189
- , the potent SERCA inhibitors, manual docking of compound 1 into SERCA followed by MD simulation (1–10 ns) was performed. For this simulation, four different complexes of SERCA and SL were chosen: i) compound 1 positioned correspondingly to the orientation of DTB in the SERCA binding cavity (simulation
Installation of -SO2F groups onto primary amides
Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186
- ][15][16][17][18][19]. Among all the developed S(VI)–F species, sulfonyl fluoride (RSO2F) was specifically recognized as unique scaffold for covalent protein inhibitors and biological probes with the affinity-driven activation for forming covalent linkages with the amino acid residues of protein
- binding sites (Figure 1) [20]. The smallest member of this family, methyl sulfonyl fluoride (MSF), is known as a selective and irreversible inhibitor of acetylcholinesterase (AChE) [21][22]. The sulfonyl fluoride inhibitors NSC 127755 was found for specifically modifying tyrosine-31 of DHFR in chicken
- aromatic amines with SO2F2 or the fluorosulfurylimidazolium salt have been achieved for assembly of N-sulfonyl fluorides [1][30], which have served as important active precursors for the development of noncovalent inhibitors (Scheme 1, (1)) [1][30][31]. Amides are the key connections in proteins, amides
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