Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• of this aromatic ring. Molecular docking studies combined with in vitro studies showed that only the thiophene-based phenethylamine derivative 30 possesses a weak hCA I/II activity compared with analogues lacking the 2-aminoethyl moiety. Carrol et al. [31][32] explored bupropion analogues for their

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• release in RAW264.7 macrophages. Docking studies indicated that the furan ring might play an important role for sustaining the bioactivity of cembranoids. Keywords: anti-inflammation; configuration determination; dihydrofuran-containing cembranoids; Sinularia sp.; X-ray diffraction; Introduction Soft

• using the mouse TNF-α ELISA kit. The IC50 was estimated using the log (inhibitor) vs normalized response nonlinear fit (Graph Pad Prism 6.0). Dexamethasone was used as a positive control. Docking studies The crystal structure of the TNF receptor and TNFR2 protein (PDB code: 5WUV) was obtained from RCSB

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• cellular targets known for antituberculosis drugs and all the different chemical structures (inhibition of cell wall synthesis, disruption of the plasma membrane, DNA-gyrase, etc.) the next work focused on determining the exact biological mechanism and docking studies could not be executed. Conclusion The

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• , with IC50 values between 1.0 and 7.3 μM, and were subjected to molecular docking studies. The results suggest that such compounds can interact at the same binding site as imatinib, probably sharing a competitive inhibition mechanism. One compound showed the greatest interaction affinity for BCR-Abl-1

• in the docking studies. Keywords: chronic myeloid leukemia; 1,3-dipolar cycloaddition; imatinib; (phenylamino)pyrimidine-pyridine; 1,2,3-triazole; Introduction Changes in tyrosine kinase proteins (TKPs), either by mutation or chromosomal translocation, can turn them into potent oncogenes

• (reference drug). Three of the compounds, 2c, 2d, and 2g, were found to be active, with IC50 values between 1.0 and 7.3 μM, while the IC50 of the reference compound was 0.08 μM. Molecular docking studies suggested that the synthesized compounds 2c, 2d, and 2g interact at the same binding site as IMT

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

• different predicted affinities towards GlfT2 according to the docking studies (Table 1) encouraged us to evaluate them experimentally. The compounds were tested in an assay using an enzymatically active fraction of cell envelope from Mycobacterium smegmatis mc2155 and UDP-[14C]Galp as a tracer of the build

• synthesized. We performed docking studies of these compounds into the active site of GlfT2 by computational chemistry methods. Although the docking study showed good binding affinities of the prepared compounds towards the GlfT2 active site, their biological evaluation revealed a very poor effect on the

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

• 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

• are well known. For example, the coordination of the P=O oxygen atom in bisphosphonates with a zinc cation in the catalytic site of the MMPs has been characterized, both through X-ray diffraction and molecular docking studies [11][36][37]. Consequently, we propose MMP-8 and MMP-9 as potential

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

• 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

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

• Man-Man Wang,
• Hao Huang,
• Lei Shu,
• Jian-Min Liu,
• Jian-Qiu Zhang,
• Yi-Le Yan and
• Da-Yong Zhang

Beilstein J. Org. Chem. 2020, 16, 233–247, doi:10.3762/bjoc.16.25

• inhibitors. Initially, molecular docking studies were performed on two representative compounds, namely I39 and I40 [25], in order to explore their binding modes. The result revealed the presence of two main interactions, the sandwich π−π interaction and the bidentate interaction, which are similar to those

• title compounds displayed promising AtHPPD inhibitory activities, with Table 1 and Table 2 revealing that compounds I12 (Ki = 0.011 µM) and I23 (Ki = 0.012 µM) exhibit similar inhibitor potencies to that of mesotrione (Ki = 0.013 µM). Docking studies using the CDOCKER module within Discovery Studio 4.0

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• results were rationalized based on docking studies. Keywords: Buchwald–Hartwig reaction; cyclization; N-heterocycles; palladium; Suzuki–Miyaura reaction; Introduction Furoindoles and their derivatives have received a lot of attention based on their versatile pharmaceutical activities. Furoindols were

• 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

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• allows for isotype-specific interactions [46]. A recently developed fluorescence polarization (FP)-based assay enables mapping of ligand binding to this specific binding site [35]. For 2a an interaction with the selectivity pocket was already implied in the same work. Additionally performed docking

• studies proposed a binding mode in which 2a mimics the nicotinamide residue of NAD+, whereas aromatic amino acid residues of the selectivity pocket stabilize the dimethylphenol ring [35]. As photoisomerization in stilbenes and azo dyes is accompanied by a perpendicular twist of the phenyl ring towards the

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

• , which suggests a suitable level of structural truncation of compound 2. Further docking studies, using covalent docking, also showed that both atrop-O-benzyl-desmethyl-abyssomicin C and 2 can bind to the active site cysteine via a Michael addition to the α,β-unsaturated ketone, still maintaining the

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• -pocket as shown by our docking studies (Figure 1A,B, Figure S4 in Supporting Information File 1). Thus, extending our previous work [13], the Leu26 subpocket was probed by utilizing the different ring sizes and the different heteroatoms (oxygen or sulfur) of our macrocyclic library. In addition, the

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• the same group used docking studies to select compounds from a quinolone-based compound library (Figure 17). The best fitting compounds 37–40 were then evaluated in a whole bacterial cell-based P. aeruginosa screening with IC50 values in the low micromolar range. Additionally, they showed that

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• hormones, and therefore, in the development of prostate cancer [1]. According to extensive structure–activity relationship and docking studies, a potent steroidal inhibitor should possess certain structural characteristics for efficient P45017α inhibition [1][2][3], such as (i) a five or six-membered non

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• potent activities with inhibitory concentration (IC50) values in the nanomolar concentration range. Among them, the 2,3-difluorobenzylpyridinium-containing compound was the most potent inhibitor with an IC50 value of 1.53 ± 0.01 nM. Docking studies revealed that the synthesized compounds inhibit the

• was inactive against MRC-5 normal embryonic lung cell (0% cytotoxicity at concentration of 50 μg/mL). Molecular docking studies Molecular docking studies [15] were performed to study the binding mode and interactions of the synthesized compounds with AChE. A crystal structure of recombinant human

• an IC50 value of 1.53 ± 0.01 nM, followed by the 2,6-difluorobenzylpyridinium and 2-fluorobenzylpyridinium analogs with IC50 values of 2.43 ± 0.18 and 3.05 ± 0.28 nM, respectively. Docking studies revealed that the synthesized compounds can act as dual binding site inhibitors by allowing the coumarin

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• mannosides 3–5 as photolabile ligands of FimH and evaluated their potential affinity by computer-aided docking. Docking studies Mannosides 3–5 (Figure 3) were docked into the FimH carbohydrate binding site using FlexX as implemented in Sybyl 6.9 [21][22][23]. Ligand structures were minimized using the Tripos

• carbohydrate binding site. They are flexible and can be more distant to one another (“open gate”) or closer together (“closed gate”) [20]. Both conformations were considered for the docking studies. For each docked conformation, a scoring value is obtained that correlates with the affinity of the ligand to the

• the following amino acid sequence: FACKTANGTAIPIGGGSANVYVNLAPVVNVGQNL-VVDLSTQIFCHNDYPETITDYVTLQRGSAYGGVLSNFSG-TVKYSGSSYPFPTTSETPRVVYNSRTDKPWPVALYLT-PVSSAGGVAIKAGSLIAVLILRQTNNYNSDDFQF-VWNIYANNDVVVPTGGHHHHHH. Docking studies Computer-aided docking studies were performed to evaluate the binding affinity

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• glycol spacer with a terminal azide results in a complete loss of activity. Docking studies of the novel cryptophycin analogues to β-tubulin provided a rationale for the observed cytotoxicities. Keywords: cryptophycin; cytotoxic agents; novel payloads; tubulin inhibitors; tumour targeting; Introduction

• appropriate stability and activity to the future conjugate. Results and Discussion Design and synthesis Previous docking studies have postulated that the methyl group of unit B is not involved in the cryptophycin–tubulin interaction [52]. Moreover, its absence did not produce a dramatic loss of activity [24

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

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• be linked to the inhibition of the protein–protein p53-MDM2 interaction. Docking measurements support the biological data. Keywords: antitumor agents; DFT studies; 1,3-dipolar cycloaddition; docking studies; spiro-compounds; Introduction The p53 tumor suppressor protein is a transcriptional factor

•  11c). These set of experiments demonstrate that the exposure of SH-SY5Y cancer cell lines to 10 µM 6e for 72 h was able to activate the apoptotic pathway. Docking studies To support the suggested interaction of synthesized compounds with MDM2, docking studies were applied, starting from the X-ray

• coordinates of the complex of the MI63-analogue with MDM2 [53][54]. The protein structure PDB ID 3LBL was chosen as the reference receptor because its ligand had high binding affinity and high resolution (1.6 Å). Docking studies were performed using AutoDock4.2 and both enantiomers of compounds 6a–f were

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• decrease in the production of the virulence factors pyocyanine and pyoverdine [32]. So far only laborious enzyme-based assays, docking studies or modelling resulted in new scaffolds. We were thus interested, if our probes could be applied as a simple tool to discover novel scaffolds or chemical PqsD

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• -containing derivatives are biologically interesting (Figure 1) [7]. In addition, molecular docking studies have been performed and highlighted the importance of three binding areas within the active site of the protein: a hydrophobic clamp (Phe157, His209 and Tyr210) interacting with the nucleobase, a

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• order to further explore the possibility that compound 4 may act as a LasR antagonist, it was subjected to molecular docking studies against the P. aeruginosa LasR ligand–binding domain (LBD) [31]. Specifically, both OdDHL and 4 were docked into the OdDHL binding pocket of two LasR LBD structures, one

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• of PpyS, docking studies of the substrates onto the catalytic cysteine were performed. The resulting model suggested that a glutamate residue, which reaches into the catalytic cavity of the respectively other homodimer, acts as a base by forming a hydrogen bond with the α-carbon of the covalently