Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• on LPS-induced nitric oxide production in RAW 264.7 macrophages. Keywords: lignan derivatives; nitric oxide production inhibition; norlignans; Selaginella sinensis; Introduction Selaginella is the only genus of Selaginellaceae. As a representative of the earliest and still-surviving vascular plant

• control. As a result, compounds 1, 2, 4, and 5 showed mild inhibitory activities with inhibition rates in the range of 9.47–18.75%, compound 3 showed moderate activity with an inhibition rate of 42.06 ± 2.02% at a concentration of 50 μM (ʟ-NMMA, 59.31 ± 2.19%, Table 2). Conclusion In summary, three new

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• of antivirals which solely target the dengue virus via the inhibition of an essential interaction between the viral proteins NS3 and NS4B [200]. Still in the domain of infectious diseases, there are two very advanced public-based endeavors aiming at providing drugs against malaria which are

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• growth retardation of the Gram-positive species Bacillus subtilis 168 and Acinetobacter baumannii 09987 (Figure 3A and B). However, growth inhibition was not strong enough to yield a clear MIC value, as the determination of a MIC requires complete inhibition of visible bacterial growth and residual

• /mL), a MIC of 128 mg/mL was achieved (Figure 3C). We also investigated whether the reported inhibition of glutathione S-transferase [11] is a result of a Michael addition of glutathione to TDD. However, no reaction occurred between glutathione and TDD in DMF/H2O (1:1) under prolonged stirring at room

• inactivity of 4 against bacteria was confirmed in this study, and also 2 is an inactive metabolite of S. spectabilis, while for 1 moderate growth retardation against A. baumannii and B. subtilis, and growth inhibition against PMBN-treated E. coli was observed. However, the low activity of 1 in these assays

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• mL MeOH was added and the mixture was treated with ultrasound for 15 min. After centrifugation, the supernatant was directly analyzed by HPLC following analytical method A. Chemical genetics experiments All samples involved in inhibition experiments were set up using 100 mL flasks containing 20 mL

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• formation from tetrazolo[1,5-a]quinoxalines 1 is still limited. Triazole-linked N-heterocycles like pyridotriazoles and quinolinotriazoles exert a variety of favorable biological properties like anticancer and antimicrobial activities as well as protein kinase inhibition [10][13][14][15]. Moreover, a vast

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

• anti-inflammatory activity by the inhibition of LPS-induced TNF-α and CCL2 release in RAW 264.7 macrophages. Keywords: Acanthella cavernosa; anti-inflammatory; biosynthetic pathway; chiral separation; marine sponge; sesquiterpenoid; Introduction Marine sponges of the genus Acanthella (class

• 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

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• the IC50 values for compounds 12–18, which differ only in the substituent at the second position of the pyrimidine ring, reveals that the presence of a methylthio group at this position gives compound 12 a slight advantage in the inhibition of the HDAC4 isoform, while the presence of a more bulky

• substituent at the second position of the pyrimidine ring favors the inhibition of HDAC8 isoforms (Table 2, compounds 13–15 and 17). However, most of the compounds tested, with the exception of 29, were inactive or showed weak inhibitory effect on the HDAC4 isoform. Comparison of the potency of the HDAC8

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• in other foodstuff such as fish and coffee contaminations with 1 are perceived as unpleasant flavor constituents [15][16][17][18]. Despite its occurrence in fungi, 1 also has moderate antifungal activity as observed for its inhibition of mycelial growth and sporulation in Fusarium moniliforme [19

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• against the pathogenic fungal strains Aspergillus fumigatus and Candida albicans. The sensitivity of the organisms was assayed against the activity of tested compounds solutions (at 10 mg/mL concentration) using a modified agar well diffusion method with determination of the inhibition zone diameter in mm

• was confirmed by the MIC values measured by the broth microdilution method by recording the lowest concentration that showed inhibition of microbial growth (Table 2). The results of the determined MIC values showed the same trend of the antimicrobial activities explored by determination of the

• inhibition zone diameter using the agar well diffusion method. The structure–activity relationship (SAR) elaborated that piperazines with aliphatic groups on the nitrogen atom are more active than those with aromatic substituents against the fungus C. albicans. On the other hand, compounds comprising

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• replicating their structures). The structural dissimilarity between the reactants and the subsequent product often contributes to the successful release of the product from the reaction vessel, thus, reducing product inhibition. Hence, it can be envisioned that the introduction of functionality within the

• product inhibition, and b) higher nanomechanical speed enlarges catalyst liberation. While the development of multicomponent rotors has started almost 20 years ago with seminal works by Shionoya [78][79][80] and Kume [81][82], the fascinating prospects of discrete nanomechanical motion was impressively

• geometrical or constitutional situation at the binding sites [92]. In a detailed recent study, the finding of a Hammett correlation in such nanorotors corroborated that a rate-determining dissociation at the rotator–metal binding interaction dictated the rotational speed [93]. Reducing Product Inhibition (RPI

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• pressure on the inhibition by pyruvate was measured and is shown in Figure 9. The value for the inhibition constant is in the same order of magnitude as results of other groups, measured at ambient pressure (0.146 ± 0.019 mol/L [5]). Since the KI value changes with pressure (Table 4), the concentrations

• were kept constant and only the pressure was varied, resulting in the reactions rates shown in Figure 10 (left). By rearranging the rate expression and inserting the previously calculated kinetic parameters, the inhibition constant was calculated (Figure 10 (right)). The change in molar volume

• suggests a reduction in molar volume. The circular reactor setup allowed for easy sampling and enabled the analysis of the resulting progress curve. The findings for the epimerase indicate that some inconspicuous reactions, such as the inhibition by pyruvate, can be influenced by pressure. In both

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• oxygen with sulfur. In particular, we present synthetic procedures toward bioisosteres of karrikins with one or two sulfur heteroatoms incorporated into the core backbone together with evaluation of their biological activity in inhibition of acetylcholinesterase. Keywords: acetylcholinesterase

• brain of patients suffering with the Parkinson’s and the Alzheimer’s disease, respectively. Therefore, research is focused on the discovery of new drugs protecting acetylcholine and dopamine levels via inhibition of acetylcholinesterase (AChE) and monoamine oxidase (MAO). A promising source of such

• derivatives 27–30 were prepared from 8, 20, 21, and 26 using microwave heating with Lawesson’s reagent and HMDO (Scheme 6). Thionation provided the title compounds in good to high yields. Biochemical study – AchE inhibition The compounds were further tested for their ability to inhibit AChE in vitro [24

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• ). The compounds with the highest antimalarial activity were 3b, 9e, 3a, and 10d with EC50 values of 0.2 ± 0.1 µM, 0.2 ± 0.04 µM, 0.3 ± 0.1 µM and 0.34 ± 0.01 µM, respectively. Unsubstituted 1-(7-chloroquinolinyl)pyrazole 11 was the only compound of this series that showed no inhibition up to a tested

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• , antitubercular, antidiabetic, antibacterial as well as cholinesterase inhibition (Figure 1) [3][4][5][6][7]. These unique chemical and biological characteristics of bispirooxindoles have stimulated the concentration of the synthetic community on developing new synthetic strategies towards their synthesis [8][9

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea

• Di Zhang,
• Zhe Wang,
• Xiao Han,
• Xiao-Lei Li,
• Zhong-Yu Lu,
• Bei-Bei Dou,
• Wen-Ze Zhang,
• Xu-Li Tang,
• Ping-Lin Li and
• Guo-Qiang Li

Beilstein J. Org. Chem. 2022, 18, 374–380, doi:10.3762/bjoc.18.42

• value of 19.03 μM. The investigation of anti-inflammatory activities of lobophysterols E–H with classic transgenic fluorescent zebrafish models (Figure 5) showed that compound 1 exhibited moderate activity, with an inhibition rate of 32% (20 μM). Conclusion In conclusion, four new steroids

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• after 24 h at 60 °C. Carvone isomerization was achieved at 60 °C for 24 h only combining the use of 10 mol % of capsule and 10 mol % of HBF4. Nevertheless, the reaction under identical conditions, but in the presence of 10 equiv of 3 as competitive guest, led only to a minimal inhibition of the reaction

• ), with quantitative yield after 20 h at 60 °C in the presence of 10 mol % of the capsule. The same reaction carried out with the capsule 16 and in the presence of 3 as competitive guest led to complete inhibition of the formation of the corresponding alkene (Figure 2D, Table 2, entry 2). This provides

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• -stoichiometric quantities of hosts because of the product inhibition effect, which arose from the entropic disadvantage of the need for binding two reactant molecules [39][40][41][42][43]. In this particular report, when the octahedral cage host A was used, the Diels–Alder reaction of 9-hydroxymethylanthracene

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• sialic acid derivatives in good yields and high purity via copper-catalysed azide–alkyne cycloaddition (CuAAC, click chemistry) and evaluated their activity towards TcTS and neuraminidase. Surprisingly, the compounds showed practically no TcTS inhibition, whereas ca. 70% inhibition was observed for

• neuraminidase in relation to the analogues bearing hydrophobic substituents and ca. 5% for more polar substituents. These results suggest that polarity changes are less tolerated by neuraminidase due to the big difference in impact of hydrophobicity upon inhibition, thus indicating a simple approach to

• differences in sialidases that need to be addressed in order to achieve selective inhibition. Keywords: inhibition; neuraminidase; sialic acid; trans-sialidase; 1,2,3-triazole; Introduction Amongst the diversity of glycans present in living organisms, N-acetylneuraminic acid (Neu5Ac, sialic acid) is

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• ], compounds 1−17 were evaluated for their inhibitory activities against LPS-induced nitric oxide (NO) production in RAW 264.7 mouse macrophages. All of them showed mild inhibitory activities with inhibition rates of 10–20% at a concentration of 50 μM (Table 2). Since coumarin derivatives were reported to have

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• reactions. The chain length in 14 should generally be suitable for effective HDAC inhibition and the thioester moiety might act as a prodrug as described for the natural HDAC inhibitor largazole. Further investigations are currently in progress. Naturally occurring HDAC inhibitors. Naturally occurring HDAC

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• Qiuxin Zhang Weiyi Tan Bing Xu Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA 10.3762/bjoc.18.17 Abstract Here we report the synthesis and effect on the cell viability of pyrrole-conjugated phosphopeptides. Encouraged by the selective inhibition of cancer

• from 1, are largely compatible with HeLa cells, while 1, at 400 μM, significantly inhibits HeLa cells. These results suggest that morphological transition or extensive self-assembly triggered by enzymatic reactions likely is necessary for the inhibition of HeLa cells by EISA. This work, thus, provides

• investigated the physical properties (enzyme-catalyzed hydrogelation or supramolecular structural transformation) [62][70] and biological properties (cell viability, biostability, and cell-selective growth inhibition) [43][62] of the naphthylacetyl N-terminal-capped phosphopeptides. These studies have produced

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• ][14], ddI (didanosine) [15], d4T (stavudine) [16][17], 3TC (lamivudine) [18][19] and AZT analogues were synthesized and evaluated towards inhibition of HIV reverse transcriptase (HIV RT). However, the toxic side effects associated with these molecules and development of drug-resistant viruses

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

• evaluated against their antioxidant activity and exhibited promising activity. Protein tyrosine phosphatase 1B (PTP1B) is essential in the dephosphorylation of the activated insulin receptor, and inhibition of this enzyme would be an excellent strategy for the treatment of type 2 diabetes. Ahn and co

• -workers [82] synthesized and evaluated several 1,2-naphthoquinones substituted at position C4 with alkyl- or arylamino groups for their inhibition of the PTP1B protein. Furthermore, to discover new effective anti-inflammatory and analgesic agents, Gouda and co-workers [83] synthesized various compounds in

• intracellular ROS and includes inhibition of tubulin polymerization (Scheme 9). Semicarbazides and thiosemicarbazides are substances used to identify aldehydes and ketones, are very versatile in the synthesis of heterocycles, and have several applications in the preparation of important drugs. Nucleophilic

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• P5.2 of stapled peptide P5 shows an almost five times higher binding affinity (Kd = 258 ± 43 nM) compared to the linear reference peptide P6 (Kd = 1241 ± 162 nM, Figure 2) in the competitive FP assay. Isomer P5.1 was only isolated in insufficient amounts. Hence, a satisfactorily converging inhibition

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• inhibition upon exposure to 4-anilinoquinazolines and compounds with the same scaffolds (erlotinib, gefitinib, and verubulin), and to positive control doxorubicin (MTT assay after treatment for 72 h). Supporting Information Supporting Information File 282: Experimental procedures, characterization data