Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• relationship (SAR) studies on selective inhibitors reduce the prevalence of undesired effects, such as toxicity in mammals [4]. Despite being employed in the field for over three decades, the mode of action of preemergence herbicide cinmethylin (1, Scheme 1) has remained unknown until 2018. At that time, the

• shown good results in selectively controlling grass weeds in both cool and warm seasons [7][8][9]. Recently, it has been shown that several herbicides bearing a gem-dimethylbenzylamide motif, e.g., cumyluron (3a) and oxaziclomefone (3b), previously exhibiting an unknown mode of action, control weeds due

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• telomerase and topoisomerases I and II [15][19][20]. It is evident that the effects of berberine are not tied to any single mode of action. Chelerythrine has also been shown to possess a wide variety of biological activities, such as anticancer, antibacterial, and anti-inflammatory actions [11][21][22][23

• , while the remaining variants resulted in either equal or lower concentrations of measured ALP levels (using a Mann–Whitney U Test and a significance cutoff of P ≤ 0.05). These results suggest intercellular protein leakage is not the primary mode of action for the improved activity seen in our variants

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• noted that ELs are essential players of cell signaling [25]. Together, all these studies point out that ELs are essential for a multitude of biological functions [26] despite their mode of action is not yet fully understood. From a molecular point of view, the ether function present in alkenyl ELs

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

• temperature. Also the addition of base (NEt3) did not promote the reaction. Therefore, the mode of action of TDD towards glutathione S-transferase needs further investigation. Conclusion We have established an efficient synthesis of TDD that makes this compound available from ʟ-tryptophan with a high yield of

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

• naturally occurring HDAC inhibitors are known to date [12]. Acyclic molecules like, e.g., trichostatin A (TSA, Figure 1) were among the first isolated HDAC inhibitors. Isolated in 1976 from Streptomyces hygroscopicus by Tsuji et al. [13], TSA played an important role in rationalizing the mode of action of

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• influence on the catalytic reactions. Under ball-milling conditions, the Michael adducts were obtained in good yields but with slightly lower enantiomeric purities than in solution. DFT calculations elucidated its mode of action and confirmed a dual activation mode, which combines enamine activation of

• have evaluated the suitability of these catalysts under solvent-free conditions. With the help of DFT calculations, we elucidated the mode of action of these catalysts. Results and Discussion Synthesis of catalysts We have started the synthesis of the catalysts from Boc-protected (S)-prolinol (1), from

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• mutually very similar mode of action. Looking at the cytotoxicity dose dependence of 7, 23, and 24 on MDA-MB-231 cell line (Figure 4B), it could be seen that it is not completely linear. At a concentration greater than 1 µM, cytotoxicity did not increase at the same rate but a plateau-like curve was formed

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• for the mode of action of this cascade arylation protocol (Figure 10) [73]. In the photocatalytic cycle, the SET event between the photoexcited iridium catalyst 10-II and the substrate oxalate 33 generates a tertiary carbon-centered radical 10-IV by decarboxylation and the reduced iridium(II

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• enzymes available for polysaccharide synthesis and their mode of action was recently published [11]. Despite the numerous advantages of this approach, limited enzyme availability as well as their high specificity narrowed the substrate scope. Generally, the highly specific enzyme reactive site tolerates

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• , the natural DNA sequence had a half-life of 1 min [202]. The incorporation of fluorine at the C4' position has long constituted a challenge owing to the instability of the glycosidic bond in the resulting nucleosides. This modification is desirable due to its involvement in the mode of action of the

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• substrate. The formal language on which the method is based is a modelling language for glycosyltransferases, and can be used to classify the types of reaction catalyzed according to simple rules. We identify extension of a linear oligosaccharide as the default mode of action (Equation 1), where x and y are

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• of an in-depth understanding of their function and mode of action. Owing to the large size of biomacromolecules, the high complexity of the processes in which they participate and the natural environment in which they occur, an integrated analytical approach is often required to succeed in revealing

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

Host–guest interaction of cucurbit[8]uril with oroxin A and its effect on the properties of oroxin A

• Zhishu Zeng,
• Jun Xie,
• Guangyan Luo,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 2332–2337, doi:10.3762/bjoc.16.194

• that the molecular size of the flavonoids and the length of the sugar chains have a greater impact on the assembly mode of supramolecular systems. Results and Discussion Host–guest interactions The host–guest interaction can be effectively observed using 1H NMR spectroscopy, and the mode of action of

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• light as a cheap and economic energy source. In this way, these strategies follow the requirements of environment-friendly chemistry. Regarding intrinsic advantages as well as the complementary mode of action of the two catalytic transformations previously introduced, their merging in a synergistic dual

• synthesis. The mechanistic studies suggested a unique mode of action of this catalytic system (Figure 45). In the initial step both aromatic coupling partners coordinate to the Mn catalyst, thus generating a photoactive complex. Visible-light photoexcitation of the Ar–Mn species and subsequent electron

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• the anterior midgut of larvae [43]. Consequently, this mode of action could also be possible for fabclavines. Conclusion This study revealed a large chemical diversity for fabclavine derivatives among different Xenorhabdus strains, which is achieved by the promiscuity of single enzymes or domains

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• , Figure 5B (For the comparable results see Figure S-6.2A and B, Supporting Information File 1). The mode of action under aerobic conditions does not involve hydroxyl radicals (in fact, DMSO seems to enhance the ds nicks), Figure 5B, well 5. It is possible that excess of this solvent facilitates the

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties

• Xiaodong Zhang,
• Jun Xie,
• Zhiling Xu,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 71–77, doi:10.3762/bjoc.16.9

• the host–guest interaction packing and pattern are shown in Figure 2. 1H NMR spectroscopy is usually one of the most effective methods to characterize host–guest interactions and can be used to deduce the mode of action of the cucurbit[n]uril–guest according to the chemical shift of the proton

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• . 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

Terpenes

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 2966–2967, doi:10.3762/bjoc.15.292

• elucidation, total synthesis, biosynthetic studies, bioactivity and functionalisation for mode of action studies, and other applications of terpenes, e.g. as fragrances. I thank all colleagues who have participated in this issue for their contributions and the whole Beilstein team for the professional support

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• , no further investigations related to the conserved mode of action or toxicity were performed. Conclusion We have described the synthesis and antibacterial activity of two new truncated derivatives of AbC. Previous work indicated that the three methyl groups of AbC were not required for activity [10

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• cause nephrotoxicity [7]. The mode of action of adefovir has been widely studied and involves the inhibition of viral replication by the termination of DNA synthesis [8][9][10]. Although adefovir was described in 1986 for the first time by Holý, De Clercq and co-workers, it is still actively employed in

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• nevaltophines act as prophenoloxidase activators, it is suggested that they have a specific role in the bacteria/nematode/insect symbiosis. Little or nothing is known about the mode of action of this simple amide against S. aureus. Structure–bioactivity studies revealed that the α-keto moiety and the amide

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• use of therapeutic antisense oligonucleotides (AONs) [1][2][3][4]. These short, synthetic fragments bind through Watson–Crick base pairing to cellular RNA, thus modulating or silencing the gene expression through various mechanisms [5][6][7]. One mode of action is the recruitment of the endonuclease

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

• . aeruginosa as compared to cisplatin (Figure 1). Mode of action The growth inhibitory effects of cisplatin on both eukaryotic cells and microbial cells are attributed to the interactions of Pt(II) in cisplatin with DNA [28][29][30]. To reveal the growth arresting mechanisms and overall impact of cisplatin on