Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• cationic fluorescent peptidic β-tryptase inhibitor (peptide 9, Figure 8) [51]. The peptide is designed by attaching two Lys–Trp–Lys tripeptide units to a central lysine via the C-terminus. The N-terminus of both sides are functionalized with pyrenes. Peptide 9 exhibits pyrene monomer emission at 400 nm and

• . Thus, it acts as inhibitor by preventing the substrate to reach the active sites in β-tryptase. Confocal laser scanning microscopy (CLSM) confirms that peptide 9 is mast-cell permeable and exhibits inhibitory activity within cells by suppressing their growth (Figure 8B). Heparin detection Heparin is a

• laser scanning microscopy images of CHMAS cells treated with 10 μM peptide 9 for 30 min. Reproduced from [51], “A fluorescent light-up probe as an inhibitor of intracellular β-tryptase”, © 2014 Wang et al., licensed under a Creative Commons Attribution 3.0 Unported Licence, https://creativecommons.org

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• synthesis inhibitor (Figure 1) [10][11][12]. In addition, compounds with this structure were investigated as photoluminescent sensors [13] and have been employed to generate pincer and heterocyclic carbene ligands for transition metal catalysis [14][15]. A lot of efforts have been dedicated to the

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• actinomycete origin. For example, salinosporamide A, an antitumor drug candidate in clinical trials, is a proteasome inhibitor with an unusual γ-lactam-β-lactone bicyclic core produced by marine Salinospora tropica [10]. Abyssomicin, another example of uncommon polycyclic frameworks, is an antibacterial

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• contains the trifluoromethylpropargylamine moiety and has been developed as the inhibitor against non-nucleoside reverse transcriptase for the treatment of human immunodeficiency virus [27] (Figure 1). Thus, the development of synthetic methods for the preparation of these compounds, featuring

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• complete inhibition of BACE-1 under the conditions of the assay, giving an IC50 value of 59.2 μM. In contrast, analog 2 was a much weaker inhibitor of BACE-1, failing to achieve complete inhibition, and giving an estimated IC50 value of >1,000 μM. There are several conceivable explanations for the reversed

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• attention for potential applications in host–guest recognition, such as gas storage and cationic complexation [31][32][33]. In the past years, the recognition of the biological and pharmaceutical relevance of fullerenes, such as their photodynamic activity, phototoxicity, HIV-1 protease inhibitor ability

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• multimeric proteins like the hexameric AAA+ ATPase p97 [124]. Furthermore, methyl-TROSY-HMQC has been employed to investigate the allosteric mode of action of the synthetic inhibitor filibuvir to the selectively Ileδ1 methyl-labeled hepatitis C virus RNA polymerase NS5B [125]. This study also includes a good

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• ][20][21][22]. However, there is comparatively less precedence of lipophilicity comparisons between fluorinated isopropyl groups, cyclopropanes and oxetanes. Examples of bioactive compounds are given in Figure 2. During the optimization of the LpxC inhibitor 7a [23], it was shown that fluorination to

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• O-glycan on fibrinogen alpha chain G272GSTSYGTGSETESPR (Figure 5a). HCC patients showed a relative decrease in disialylated and an increase in monosialylated O-glycan abundance on both plasma protease C1 inhibitor V45AATVISK and histidine-rich glycoprotein S271STTKPPFKPHGSR (Figure 5b and 5c

• G272GSTSYGTGSETESPR, (b) plasma protease C1 inhibitor V45AATVISK, and (c) histidine-rich glycoprotein S271STTKPPFKPHGSR. N = 3; values show mean; error bars show standard error of the mean; *, P < 0.05. Supporting Information Supporting Information File 548: Supplementary Tables S1–S42. Supporting Information File

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• the Henry reaction, the nitroethane anion intermediate, coordinates to the Ni-porphyrin, which slows down nucleophilic addition to the nitrobenzaldehyde. Hence, the switchable catalyst 1 contains both, a catalytic center (nitrogen lone pair) and an inhibitor (Ni2+ ion). If the nitrogen lone pair

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• ; tetrahydropyranes; Introduction Сhiral phosphonates [1][2] and phosphoryl-substituted heterocycles [2][3][4] have received significant attention in recent years due to their wide range of biological activity. For example, SF-2312 (1) is a natural antibiotic – an enolase inhibitor produced by the actinomycete

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• ]. While the research suggested chemically pure lipid X had no immunostimulatory properties of lipid A, it did behave as a competitive inhibitor of LPS [13]. In this paper we describe a synthesis of lipid X (1) and the disaccharide lipid A precursor 2 (2,2′-N;3,3′-O-tetra[(R)-3-hydroxytetradecanoyl]-β(1→6

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• antiviral agents, respectively (Figure 1) [5][6]. The field of acyclonucleotides (ACN) has been explored less, however, the introduction of fluorine atoms showed remarkable effects. The most representative examples are phosphate analogues such as the nucleoside phosphorylase inhibitor III and acyclic

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• between 0.332–3.85 mM were established by a spectrophotometric assay with a purified recombinant GlfT2 enzyme, UDP-Galf as a donor substrate and analogs of the acceptor substrate [24][25][26][27][28][29][30]. The best reported IC50 value (0.180 mM) for a putative GlfT2 inhibitor was obtained for a

• synthesis of lipid-linked galactan. However, the experiments evaluating the dose effects of the predicted best (1bα) and the worst (3a) inhibitor on the mycobacterial galactan synthesis indicated the possibility of GlfT2 inhibition by 1bα at the highest tested concentration (10 mM). However, it is clear

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• [2], antitumor [3], anti-HIV [4], inhibitor of Trypanosoma brucei [5], angiogenesis inhibitor [6], antiplasmodial antifolates [7], and antimicrobial [8]. Moreover, and in particular N2,6-disubstituted-1,3,5-triazine-2,4-diamines possess a wide range of chemotherapeutic activities [8][9][10][11

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• canadine, is an isoquinoline alkaloid recurring in several plant species [55][56][57]. THBER is able to act to the central nervous system as an inhibitor [58], possesses hepatoprotective effects [59], is employed in the protection against cerebral ischemia-reperfusion injury [60], and shows anti-arrhythmic

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• topoisomerase 1 inhibitor [14] and DNA intercalator), bicolorine (5-methyl-[1,3]dioxolo[4,5-j]phenanthridin-5-ium ion, a trypanocidal) [15], and the antimalarian nitidine, as well as ethidium bromide (EB), that has been employed as a DNA- and RNA-fluorescent marker for a long time (some examples are collected

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• IV inhibitor carmegliptin (2, DPP IV) with potential for the treatment of type-II diabetes [3][4]. A comparative study on novel classes of anticancer drugs identified benzo[a]quinolizines 3 and 4 (Figure 1) to be useful for a specific inhibition of heat shock response in cancer cells, which strongly

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• as inhibitor of kinases, insecticides, and acaricides, its sulfur analogue, 6-amino-2-thiaspiro[3,3]heptane (28) was prepared from the cheap starting material 2,2-bis(bromomethyl)propane-1,3-diol (11). Compound 11 was converted into 3-(tert-butoxycarbonyl)-1,1-bis(hydroxymethyl)aminocyclobutane (25

• -bis(hydroxymethyl)indolin-2-one (51) was reacted first with mesyl chloride and then treated with sodium sulfide to afford 6-bromospiro[indoline-3,3′-thietan]-2-one (53), which was further converted into the target inhibitor candidate 54 [42] (Scheme 12). 2-Methylene-γ-butyrolactone (55) as the initial

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• describe the enzyme inhibitor site binding modes [16][17][18]. Thus, in this work, the bisphosphonates 3–6 were synthesized by a two-step method and then evaluated through two in vivo acute inflammation models in BALB/c mice. Furthermore, the acute toxicity was determined for these derivatives, and

• 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

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• different organisms, enabling researchers to identify and prioritise compounds active against multiple pathogens. For example MMV690102, which was originally developed as an inhibitor of kinetoplastid dihydrofolate reductase [159], is active against three trematode species (F. hepatica, S. haematobium, S

• follow-up study identified two additional pyrazole-5-carboxamide compounds with activity against H. contortus, although not improving on the potency of tolfenpyrad [166]. Tolfenpyrad acts in arthropods as an inhibitor of mitochondrial complex I [167]. It will be interesting if a tolfenpyrad derivative

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• able to increase the secretion of insulin by the pancreas that modulates blood sugar level when it is high. Sitagliptin was granted FDA approval in October, 2006 [116]. Retagliptin phosphate: Retagliptin phosphate (184) is under investigation as a DPP-4 inhibitor for treating type-2 diabetes. It is an

• synthesis of compound 184 [119][120] (Figure 7). Evogliptin: (R)-2,4,5-Trifluorophenylalanine 38b is required for the synthesis of evogliptin (185, Figure 8), an antidiabetic drug in the dipeptidyl peptidase-4 (DPP-4) inhibitor or "gliptin" class of drugs. The South Korean pharmaceutical company Dong-A ST

• developed evogliptin (185) and it is currently approved for use in South Korea [121][122][123]. LY2497282: Eli Lilly identified LY2497282 (186) as a potent and selective DPP-4 inhibitor, also for the treatment of type II diabetes. The inhibition of GLP-1 degradation by dipeptidyl peptidase IV (DPP-4) has

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• instance, the hydroxy group can be converted into an oxime, acyloxyimino, alkoxyimino, alkoxy and 3-oxo group [9]. As a proteasome inhibitor, compound a suppresses the chymotrypsin-like activity of the proteasome in MT4 cells with an IC50 of 0.22 μM, nearly 100-fold more potent than 18β-glycyrrhetinic acid

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• [3]. Among these drugs, panobinostat (Farydak, Novartis) an FDA approved drug, has been recognized as a pan-deacetylase inhibitor [9][10]. As a hydroxamic acid pan-HDACi, it is zinc-dependent, capable of binding in a bidentate fashion to the zinc-containing catalytic domain of the HDACs, and

• panobinostat. The reported −log(Kd) values were 8.93, 8.64 and 8.25, respectively, with panobinostat possessing a docking score of 8.47. Considering the effects of structural diversity, TOI3-rev was included in the library and computationally evaluated to determine its potential as an HDAC8 inhibitor. TOI3-rev

• panobinostat against HDAC8 have been shown to be 277 nM [11]. In vivo studies measuring the IC50 values of panobinostat have also been performed, however, since panobinostat is a pan-DAC inhibitor it has been difficult for researchers to specifically correlate its IC50 value for HDAC8 in a physiological system

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• -R indicates C to be a potent inhibitor of P). Compounds: a full range of cheminformatic analysis including 2D or 3D clustering, property prediction and chemical ontology assignments. Proteins: a full range of bioinformatic analysis including gene ontology (GO) assignments, pathway annotation