Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• A and B (54, 55), which were discovered by co-culturing Nocardia uniformis IFM0856T and J774.1 cells [124][125]. Uniformides were shown to suppress the production of nitric oxide, IL-6, and IL-1β by inhibiting the NF-κB pathway. Because NF-κB signaling plays a central role in the immune response

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• also reported to inhibit cell invasion and metastasis [54][55]. Anti-inflammation and antioxidation Crocins exhibit anti-inflammation properties by scavenging free radicals and regulating the expression of antioxidant enzymes. Crocins can inhibit the NF-κB signaling pathway, thus downregulating the

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• cell lines. The compounds were tested in five different concentrations (ranging from 1 to 100 μM) and showed no in vitro cytotoxicity. However, compound 10 was found to possess anti-inflammatory activity. It showed effects on LPS-induced activation of NF-κB and COX-2 similar to the Bay 11-7082 molecule

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• tumor necrosis factor-α (TNF-α) and C–C motif chemokine ligand 2 (CCL2) were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, using NF-κB inhibitor BAY-11-7082 as the positive control. Compound 3 displayed promising dose-dependent anti-inflammatory activity with the inhibition

• following the manufacturer’s instructions. β-ACTIN was used as the normalization control. All reactions were performed in triplicate. The NF-κB inhibitor Bay 11-7082 (5 μM) was used as a positive control. Chemical structures of compounds 1–8. ORTEP drawing of 2 (displacement ellipsoids are drawn at the 50

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• . These data indicated that 47b targets p38 kinase and NF-κB and may serve as an anti-inflammatory agent (Scheme 13). In 2020, Almeida and co-workers [92] synthesized naphthoquinone imines from β-NQSNa (18) with modifications in β-carbonyls. These compounds were obtained in a sequence of reactions

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• ELISA NF-κB assay. Upon the mitochondrial transmembrane potential assay, three members demonstrated ED50 values in the nanomolar level [4]. Moreover, three of the members were identified as inhibitors of the chemokine receptor CCR5 [11]. Therefore, they are potential agents for treating human

• ]. These seven compounds, 1–7, were also evaluated for enzyme-based ELISA NF-κB and proteasome inhibition assays (Table 2, entries 1–7), but only brevipolide G (7) and brevipolide C (3) showed significant activities with ED50 values of 15.3 and 38.0 μM, respectively (Table 2, entries 7 and 3) [4]. Lastly

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• pathways involved in the regulation of reactive oxygen species (ROS) and/or nitric oxide (NO) [9], histone methyltransferase [10], HSP70 [11], Jak2, Bcl-2/Bax [12], caspase 8 [13], NF-κB [14], X-linked inhibitor of apoptosis protein (XIAP) [15], MAPK, PI3K [16], and MPK1, ERK-1/2, and JNK-1/2 [17]. The

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• replacing the whole Mycobacterium in complete Freund’s adjuvant. MDP triggers an immune response by activating the mammalian NOD-like receptor, nucleotide binding oligomerization domain-containing protein 2 (NOD2). NOD2 is an intracellular protein that signals via the NF-κB pathway to proximally activate

Molecular basis for the plasticity of aromatic prenyltransferases in hapalindole biosynthesis

• Takayoshi Awakawa and
• Ikuro Abe

Beilstein J. Org. Chem. 2019, 15, 1545–1551, doi:10.3762/bjoc.15.157

• beneficial bioactivities, exemplified by 12-epi-hapalindole E isonitrile, which exhibits antibacterial, antifungal, and antimycobacterial activities [16], and ambiguine I, which induces apoptosis and cell-cycle arrest through the inhibition of an NF-κB-related regulation pathway [17]. To investigate their

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• extensive spectroscopic analysis and by comparison with the previously reported analogues. In a bioassay, compounds 1, 2 and 4 exhibited interesting inhibitory activities in vitro against PTP1B and NF-κB. Keywords: Clavularia viridis; Lemnalia flava; NF-κB; PTP1B; sesquiterpenoid; soft coral, terpenes

• further support of the assigned structure for 6 (Figure 1). Thus, compound 6 was determined as a C-1 isomer of ent-1-hydroxyalloaromadendrene (6a), namely, claaromadendrene. In bioassays, all the isolated compounds were tested for protein tyrosine phosphase-1B (PTP1B) and NF-κB inhibitory activity. In the

• used as positive control in this assay. In NF-κB inhibitory assay, compounds 2 and 4 showed the most potent NF-κB signaling pathway inhibition with IC50 values of 6.8 and 7.3 μM, respectively, while compound 1 showed moderate activity with an IC50 value of 19.9 μM (Table 3). Conclusion In summary

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• medicinal chemistry and biology [19][20], illustrated by the marketed drugs, e.g., alpidem, minodronic acid, olprinone, zolimidine (Figure 1) and some recent examples of the imidazopyridines inhibiting tubulin polymerization [21], NF-κB [22], aldosterone synthase [23], or autotaxin [24]. Whereas many

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• initial study for the delivery of the anticancer drug doxorubicin. Results and Discussion Peptide synthesis and analysis of the secondary structure We chose two different nuclear-targeting sequences, on the one hand the N50 peptide, which was derived from the NF-κB/p50 subunit. N50 binds the adaptor

• protein importin-α at the nuclear envelope and triggers the uptake of the transcription factor NF-κB [22][23]. As second sequence we chose the NrTP sequence, which is a designed peptide coming from the rattlesnake toxin, called crotamine [3]. For both peptides, preferential accumulation within the nuclei

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

• . designed novel polyamides, which were able to bind adjacent to the recognition sites of a broad-range of transcription factors TBP, Ets-1, LEF-1 and NF-κB [69], thereby inhibiting binding of these transcription factors to DNA and ternary complex formation [70]. Dervan et al. has further introduced a novel

• Py/Im polyamide 14 (Figure 6) that was able to bind preferentially the sequences 5′-WGGWWW-3′ and 5′ GGGWWW-3′ in the Nuclear factor κB sites, thereby reducing the expression of various NF-κB-driven genes including IL6 and IL8 [71]. Another structural analog of conjugate 11, conjugate 15 was

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• antagonist activity. On the other hand, all synthetic H. pylori lipid A and Kdo-lipid A showed IL-18 and IL-12 inducing activity, whereas the presence of Kdo decreased the potencies. Thus, it was shown that underacylated H. pylori lipid A could disrupt the TLR4-mediated NF-κB signaling by inhibiting the LPS

• -O-Alloc and 1-O-TDS) combined with acylation and regioselective anomeric phosphorylation furnished, after global deprotection, variably acylated P. gingivalis lipid A substructures 46 and 47. The synthetic compounds did not stimulate the NF-κB signaling pathway, but efficiently inhibited the LPS

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• such as flavonoids, caffeic acid derivatives and diarylheptanoids were found to have a pleiotropic influence on cellular signaling (e.g., by the inhibition of transcription factors such as NF-κB or Nrf2 [9][10], or antioxidative effects [10][11]). Furthermore, polyphenols are found in high

• demonstrated anti-angiogenic properties in in vitro and in vivo experiments. In the following years, many studies on the anti-angiogenic properties in different tumor cell lines and in animal models were reported [19][20][21][22]. They included interactions with the transcription factor NF-κB, mTOR pathway

• . KUNZE, Theaceae). It is the esterification product of epigallocatechin and gallic acid. Many studies provide evidence that EGCG modulates multiple signal transduction pathways, controlling the unwanted proliferation of cells. It inhibits the activation of HIF-1α, NF-κB and VEGF expression, thereby

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• of transcription factors including Stat3, NF-κB and the β-catenin activated T-cell factor (TCF) [17]. Constitutive activation of Stat3 by paracrine and autocrine mechanisms has been detected in diverse human cancer cell lines and tissues which contribute to oncogenesis by promoting cell proliferation

• luciferase expression with an IC50 value of 1.6 µM (0.6 µg/mL). In addition to Stat3, the response of the survivin promoter construct also depends on the transcription factor NF-κB [19] and as shown in Figure 4A, SF002-96-1 inhibited the inducible NF-κB-dependent reporter gene expression in Colo 320 cells

• compound could affect the binding of Stat3 and NF-κB to the survivin promoter in living cells, we performed ChIP assays with primers covering suggested Stat3 and NF-κB (p65) binding sites [23][24]. Q-PCR of the −1231/−1009 (primers Sat3_1), −131/+46 (primers Stat3_2) and −920/−773 (primers Stat3_3) regions

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA 10.3762/bjoc.9.103 Abstract Activation of nuclear factor-kappa B (NF-κB) and related upstream signal transduction pathways have long been associated with the pathogenesis of a variety of inflammatory

• ) initiative. The chemical probes discussed herein represent first-in-class, non-kinase-based modulators of the NF-κB signaling pathway, which were identified and optimized through either cellular phenotypic or specific protein-target-based screening strategies. Accordingly, the resulting new chemical probes

• center’s efforts. Within the realm of immunology and inflammation research, many cellular pathways leading to the activation of NF-κB family of transcription factors have been identified and several excellent reviews are available [2][3][4][5]. In general, these pathways have been shown to participate in

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• tuberculosis as well as further microbial pathogens, for activity in an antidiabetic activity assay panel, in a 3T3-L1 murine adipocyte assay, and in a NF-κB protein complex assay, but they exhibited no activity (see detailed description in Supporting Information File 1). Phthalide derivatives are compounds of

• Hepatitis B virus was performed according to Sells et al. [32] and Korba and Gerin [33]. The activity assays against two strains of antibiotic resistant Mycobacterium tuberculosis were performed according to Bauer et al. [34]. The methodology for the inhibition of the NF-κB protein complex is described by

• , Amsterdam, Netherlands) for performing the M. tuberculosis activity assays, Dr. Marc Diederich (Fondation Recherche sur le Cancer et les Maladies du Sang Laboratoire de Biologie Moleculaire et Cellulaire du Cancer (LBMCC), Luxembourg) for performing the NF-κB activity assays and Dr. Steinar Paulsen

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• oligonucleotides can also serve as a tool for the investigation of interactions between NF-κB proteins (NF-κB is a protein complex that controls the transcription of DNA and plays a key role in regulating the immune response to infection). A study was reported by Kittaka and co-workers [38] which described an