Design, quality and validation of the EU-OPENSCREEN fragment library poised to a high-throughput screening collection

RSC Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 15(4), P. 1176 - 1188

Published: Jan. 1, 2024

The process by which researchers from all over the world can apply for projects using EFSL poised to ECBL at EU-OPENSCREEN screening facilities and optimize hits identified through our network of chemistry partners.

Language: Английский

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Active learning driven prioritisation of compounds from on-demand libraries targeting the SARS-CoV-2 main protease

Digital Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Software for building congeneric series of compounds in protein binding pockets is interfaced with active learning and searching on-demand chemical libraries to automate the de novo design targeting SARS-CoV-2 main protease.

Language: Английский

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New derivatives based on zerumbone scaffold as anticancer inhibitors: Synthesis, in vitro anticancer evaluation, docking, and MD simulation studies

Journal of Chemical Research, Journal Year: 2025, Volume and Issue: 49(1)

Published: Jan. 1, 2025

A three-step procedure was applied to synthesize seven novel zerumbone ethers 7a–g with N-(4-hydroxybenzyl) benzamide, substituted and cinnamamide moieties, including simultaneous O- N-acylations, ester hydrolysis, O-alkylation. The structure of intermediates target compounds elucidated using one-dimensional two-dimensional nuclear magnetic resonance, high-resolution mass spectrometry data. Their cytotoxic activities were screened on three human cancer cell lines HepG2, LU-1, HeLa. results showed that exhibited activity against all tested IC 50 values ranging from 1.71 6.86 µM stronger than zerumbone, approximately 10–35 folds. Theoretically, the mode their anticancer action studied based predicting ability inhibit Fibroblast Growth Factor Receptor 1 Vascular Endothelial 2 proteins docking molecular dynamic simulation studies. interaction important amino acids in active binding sites protein 2, Umbrella Effect formation explained significant improvement compared parent compound zerumbone.

Language: Английский

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New Isoxazoline Cyclopropyl-Picolinamide Derivatives as Potential Insecticides

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Isoxazoline insecticides exhibit broad-spectrum insecticidal activity against insect pests. However, the high toxicity to honeybees limits their application in pest management. To explore reducing of isoxazoline derivatives bees, a series new cyclopropyl-picolinamide were designed and synthesized. Bioassays revealed that FSA37 showed excellent Plutella xylostella, Spodoptera litura, exigua, with LC50 values 0.077, 0.104, 0.198 mg/L, respectively. These results surpass those fluxametamide, which displayed 0.605, 0.853, 1.254 mg/L. Furthermore, exhibited notable Solenopsis invicta. Importantly, bee studies indicated possesses significantly lower acute oral compared fluralaner fluxametamide. Quantum chemical calculations molecular docking suggest fragment may be crucial for both biological safety nontarget organisms. In conclusion, represents promising candidate highly effective environmentally friendly insecticide.

Language: Английский

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CAL-B promoted amidation of ( S )-ibuprofen: Mechanistic study and in vitro versus in silico evaluation of the anti-inflammatory activity

Biocatalysis and Biotransformation, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 18

Published: April 22, 2025

Language: Английский

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New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies

Molecules, Journal Year: 2023, Volume and Issue: 28(14), P. 5389 - 5389

Published: July 13, 2023

The development of novel scaffolds that can increase the effectiveness, safety, and convenience medication therapy using drug conjugates is a promising strategy. As result, are an active area research in medicinal chemistry. This demonstrates acetamide–sulfonamide scaffold preparation after conjugation ibuprofen flurbiprofen with sulfa drugs, these were then screened for urease inhibition. newly designed confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, elemental analysis. Ibuprofen conjugated sulfathiazole, sulfadiazine, sulfamethoxazole found to be potent demonstrated competitive mode inhibition, IC50 (µM) values 9.95 ± 0.14, 16.74 0.23, 13.39 0.11, respectively, inhibition 90.6, 84.1, 86.1% respectively. sulfanilamide, sulfamerazine, sulfacetamide, whereas sulfacetamide exhibited mixed Moreover, through molecular docking experiments, receptor-binding mechanisms inhibitors anticipated, stability analysis MD simulations showed compounds made stable complexes respective targets no conformational changes occurred during simulation. findings demonstrate approved therapeutic molecules may result classes pharmacological agents treatment various pathological conditions involving enzyme.

Language: Английский

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Design, Synthesis, and Anticancer and Antibacterial Activities of Quinoline-5-Sulfonamides

Molecules, Journal Year: 2024, Volume and Issue: 29(17), P. 4044 - 4044

Published: Aug. 26, 2024

A series of new unique acetylene derivatives 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide

Language: Английский

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Unveiling the anti-cancer potentiality of phthalimide-based Analogues targeting tubulin polymerization in MCF-7 cancerous Cells: Rational design, chemical Synthesis, and Biological-coupled Computational investigation

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 153, P. 107827 - 107827

Published: Sept. 18, 2024

Language: Английский

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Exploring the potential of propanamide-sulfonamide based drug conjugates as dual inhibitors of urease and cyclooxygenase-2: biological and their in silico studies

Frontiers in Chemistry, Journal Year: 2023, Volume and Issue: 11

Published: Aug. 3, 2023

Derivative synthesis has been a crucial method for altering the effects of already-approved medications, especially to lessen adverse and enhance results. Making use this multi-target approach, series naproxen-sulfa drug conjugates was designed synthesized. The newly were confirmed by spectroscopic techniques like IR, 1HNMR, 13CNMR, elemental analysis. screened anti-inflammatory, urease, cyclooxygenase-2 (COX-2) inhibition. Naproxen conjugated with sulfanilamide, sulfathiazole, sulfaguanidine found potent showed competitive mode urease inhibition, IC50 (µM) values 6.69 ± 0.11, 5.82 0.28, 5.06 0.29, respectively. When compared other conjugates, naproxen-sulfamethoxazole conjugation better anti-inflammatory action inhibiting induced edema 82.8%, which is comparable medication indomethacin (86.8% inhibition). Whereas it exhibited 75.4% inhibition COX-2 at 10 µM concentration reference (celecoxib, 77.1% Moreover, binding modes inhibitors receptor predicted through molecular docking studies their stability analysis MD simulations that these compounds made stable complexes respective targets there no conformational changes occurred during simulation. obtained results approved therapeutic molecules may lead development novel types pharmacological agents in treatment several pathological disorders where enzymes are involved.

Language: Английский

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Iron-Catalyzed Synthesis of Conformationally Restricted Bicyclic N-Heterocycles via [2+2]-Cycloaddition: Exploring Ring Expansion─Mechanistic Insights and Challenges

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(9), P. 6416 - 6429

Published: April 25, 2023

We present an efficient iron-catalyzed method for synthesizing conformationally restricted cyclobutane-fused N-heterocycles from unactivated precursors. This is orthogonal to the established photocatalytic methods, extends range of substrates, and provides a single-step route previously unattainable piperidines azepanes. Ring stereochemistry depends on size, with five- six-membered rings adopting cis configuration seven-membered preferring trans configuration. A key aspect this use catalyst design based electron-deficient, redox-active, pyrimidinediimine scaffold. Mechanistic investigations suggest that π-acidic core significantly enhances stability against deleterious intramolecular C–H activation pathways, while electron-rich flanking groups accelerate reaction rate. insights were obtained by extracting kinetic profiles establishing catalyst–activity relationships. Computational studies oxidative cyclization step proceeds highest energy barrier, which further confirmed experimental Hammett analysis.

Language: Английский

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