jablonkagroup/rise_ai_scientists huggingface dataset:
Authors: György G. Ferenczy | Ünige Murvai | Lívia Fülöp | Miklós Kellermayer
Source: International Journal of Molecular Sciences (article, 2024-09-28)
Field: Materials Science — Biomaterials

Mica Lattice Orientation of Epitaxially Grown Amyloid β25–35 Fibrils β-amyloid (Aβ) peptides form self-organizing fibrils in Alzheimer's disease. The biologically active, toxic Aβ25-35 fragment of the full-length Aβ-peptide forms a stable, oriented filament network on the mica surface with an epitaxial mechanism at the timescale of seconds. While many of the structural and dynamic features of the oriented Aβ25-35 fibrils have been investigated before, the β-strand arrangement of the fibrils and their exact orientation with respect to the mica lattice remained unknown. By using high-resolution atomic force microscopy, here, we show that the Aβ25-35 fibrils are oriented along the long diagonal of the oxygen hexagon of mica. To test the structure and stability of the oriented fibrils further, we carried out molecular dynamics simulations on model β-sheets. The models included the mica surface and a single fibril motif built from β-strands. We show that a sheet with parallel β-strands binds to the mica surface with its positively charged groups, but the C-terminals of the strands orient upward. In contrast, the model with antiparallel strands preserves its parallel orientation with the surface in the molecular dynamics simulation, suggesting that this model describes the first β-sheet layer of the mica-bound Aβ25-35 fibrils well. These results pave the way toward nanotechnological construction and applications for the designed amyloid peptides. Mica ; Fibril ; Antiparallel (mathematics) ; Crystallography ; Molecular dynamics ; Amyloid fibril ; Biophysics ; Protein filament ; Collagen fibril ; Materials science ; Atomic force microscopy ; Chemistry ; Chemical physics ; Nanotechnology ; Amyloid β ; Composite material ; Physics ; Biology Supramolecular Self-Assembly in Materials ; Alzheimer's disease research and treatments ; Protein Structure and Dynamics
Authors: Jaganathan Lakshmanan | Vaitheesh Jaganathan | Boachun Zhang | G T Werner | Tyler A. Allen | David J. Schultz | Carolyn M. Klinge | Brian G. Harbrecht
Source: Anti-Cancer Agents in Medicinal Chemistry (article, 2024-10-21)
Field: Chemistry — Inorganic Chemistry

Anticancer Properties Against Select Cancer Cell Lines and Metabolomics Analysis of Tender Coconut Water TCW and its components exhibit anti-cancer effects. TCW inhibits the viability of HepG2 hepatocellular carcinoma cells by reversing the EMT process through inhibition of AKT and ERK signalling. Cancer cell lines ; Metabolomics ; Chemistry ; Biotechnology ; Computational biology ; Cancer cell ; Cancer ; Biology ; Bioinformatics ; Genetics Coconut Research and Applications ; Protein Hydrolysis and Bioactive Peptides ; Plant-Derived Bioactive Compounds
Authors: Nur Pasca Aijijiyah | Reni Rahayu | Alfatchu Srilistiani | Farah Mahzumi | Tinezsia Aulia | Liangga Santoso | Lukman Atmaja | ‪Eko Budi Santoso‬ | Arif Fadlan | Mardi Santoso
Source: Journal of Applied Pharmaceutical Science (article, 2024-01-01)
Field: Chemistry — Organic Chemistry

Cinnamate-amine hybrids: Antituberculosis activity and molecular docking Antituberculosis activity and molecular docking experiments were performed on 14 cinnamate-amine hybrids. Cinnamamides 1a,b,c,d,i,j effectively inhibited the growth of Mycobacterium tuberculosis H37Rv, with cinnamamide 1c having the highest inhibition effects with a minimum inhibitory concentration value of 3.13 μg/ml. Based on the docking results, the molecule of cinnamamide 1c (binding energy of −4.13 kcal/mol) was found to be stretched from the edge of the active site to its sub-binding pocket, referred to as an extended conformation when binding to the InhA active site. Cinnamamide 1c turned out to be an inhibitor whose potency is unaffected by the conserved interaction network with the catalytic residue Tyr158. These findings suggest these cinnamate-amine hybrids as potential lead compounds in developing new antituberculosis drugs. Hybrid ; Docking (animal) ; Amine gas treating ; Chemistry ; Combinatorial chemistry ; Stereochemistry ; Biology ; Organic chemistry ; Medicine ; Veterinary medicine ; Botany Synthesis and biological activity ; Synthesis and Reactivity of Heterocycles ; Phytochemistry Medicinal Plant Applications
Authors: Katarina Magdalenić | Donatien Morillon | Steven De Jonghe | Leentje Persoons | Dominique Schols | Kristof Van Hecke | Charlotte Grootaert | John Van Camp | Matthias D’hooghe
Source: Journal of Heterocyclic Chemistry (article, 2024-12-01)
Field: Chemistry — Organic Chemistry

Synthesis and Cancer Cell Cytotoxicity of 6‐, 7‐, or 8‐Substituted 2‐(Hetero)aryl‐4‐(4‐(Hetero)aryl‐2‐Oxobut‐3‐en‐1‐Ylidene)Benzothiazepanes ABSTRACT Cancer chemotherapy is continuously challenged by serious complications like pronounced side effects and multidrug resistance (MDR). Natural products, such as curcumin, offer promising alternatives due to their diverse biological applications and low toxicity. However, curcumin's clinical utility is limited by poor bioavailability, rapid metabolism, and non‐specific (PAINS) activity. Building on previous findings, this study explored the structural modification of curcumin‐inspired benzothiazepane derivatives in an attempt to enhance their therapeutic potential through modifications of the two peripheral (hetero)aromatic rings and the benzothiazepane scaffold. In this way, eight new 2‐(hetero)aryl‐4‐(4‐(hetero)aryl‐2‐oxobut‐3‐en‐1‐ylidene)benzothiazepanes and two 4‐thiobutan‐2‐one “double Michael addition” derivatives were synthesized and tested for cytotoxicity against a panel of eight cancer cell lines. The screening results indicated that bis‐(4‐hydroxyphenyl) analogs bearing a chlorinated benzothiazepane ring exhibited the highest potency and broad‐spectrum activity at the low micromolar range. Bis‐substitutions with 3‐pyridinyl and 2‐furyl groups showed less potent but more specific activity profiles, potentially reducing PAINS effects. 2‐Aminothiophenol‐derived double Michael addition products demonstrated increased broad‐spectrum activity, highlighting the importance of the free aniline amino group for targeted effects. This study underscores the potential of benzothiazepane derivatives as viable cancer cell cytotoxic agents and provides useful insights for future optimization and evaluation. Chemistry ; Aryl ; Cytotoxicity ; Stereochemistry ; Organic chemistry ; In vitro ; Biochemistry Synthesis and biological activity ; Synthesis of Organic Compounds ; Multicomponent Synthesis of Heterocycles
Authors: Thamina Akther | William M. McFadden | Huanchun Zhang | Karen A. Kirby | Stefan G. Sarafianos | Zhengqiang Wang
Source: Medicinal Chemistry Research (article, 2024-09-14)
Field: Chemistry — Organic Chemistry

Quinazolinone-based subchemotypes for targeting HIV-1 capsid protein: design and synthesis Capsid ; Chemistry ; Quinazolinone ; Human immunodeficiency virus (HIV) ; Virology ; Computational biology ; Combinatorial chemistry ; Biochemistry ; Biology Quinazolinone synthesis and applications ; HIV/AIDS drug development and treatment ; Bacteriophages and microbial interactions
Authors: Vipin A. Nair | Aiyagala M.M. Mallikarjunasawamy | Praveen Naik | Bharath Kumar Momidi | Kuruvalli Gouthami | Vaddi Damodara Reddy
Source: Organic Communications (article, 2024-12-30)
Field: Chemistry — Organic Chemistry

Synthesis and antimicrobial evaluation of 2-thioxoimidazolidinone derivatives The infectious diseases caused by antimicrobial pathogens are often difficult to treat and thwarted by resistance to drugs.Therefore, designing new drugs to treat antimicrobial infections is a challenge in drug discovery research.A series of 2-thioxoimidazolidinone derivatives were synthesized in high yield from N'arylideneamino-2-thioxoimidazolidin-4-ones using propionyl chloride and triethyl amine in toluene medium.The compounds were screened for the in vitro antifungal and antibacterial activities.The studies revealed that compounds ()1,1'-(3-(((1E,2E)-3-(2-methoxyphenyl)allylidene)amino)-4-oxo-2-thioxoimidazolidine-1,5-diyl)bis(propan-1-one) and ()1,1'-(3-((2,4-dichlorobenzylidene)amino)-4-oxo-2-thioxoimidazolidine-1,5-diyl)bis-(propan-1-one) possess antifungal properties comparable to the reference drug ketoconazole.This study highlights the importance of substituted 2-thioxoimidazolidinone derivatives, and their potential as antimicrobial agents. Antimicrobial ; Combinatorial chemistry ; Chemistry ; Organic chemistry Synthesis and biological activity ; Synthesis and Reactivity of Sulfur-Containing Compounds ; Synthesis of heterocyclic compounds
Authors: Yoshimi Shoji | Y. Terashima | Kei Ohkubo | Hiromu Ito | Kouichi Maruyama | Shunichi Fukuzumi | Ikuo Nakanishi
Source: International Journal of Molecular Sciences (article, 2024-04-17)
Field: Chemistry — Organic Chemistry

Scandium Ion-Promoted Electron-Transfer Disproportionation of 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-Oxide (PTIO•) in Acetonitrile and Its Regeneration Induced by Water 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO<sup>•</sup>), a persistent nitronyl nitroxide radical, has been used for the detection and trapping of nitric oxide, as a redox mediator for batteries, for the activity estimation of antioxidants, and so on. However, there is no report on the reactivity of PTIO<sup>•</sup> in the presence of redox-inactive metal ions. In this study, it is demonstrated that the addition of scandium triflate, Sc(OTf)<sub>3</sub> (OTf = OSO<sub>2</sub>CF<sub>3</sub>), to an acetonitrile (MeCN) solution of PTIO<sup>•</sup> resulted in an electron-transfer disproportionation to generate the corresponding cation (PTIO<sup>+</sup>) and anion (PTIO<sup>-</sup>), the latter of which is suggested to be stabilized by Sc<sup>3+</sup> to form [(PTIO)Sc]<sup>2+</sup>. The decay of the absorption band at 361 nm due to PTIO<sup>•</sup>, monitored using a stopped-flow technique, obeyed second-order kinetics. The second-order rate constant for the disproportionation, thus determined, increased with increasing the Sc(OTf)<sub>3</sub> concentration to reach a constant value. A drastic change in the cyclic voltammogram recorded for PTIO<sup>•</sup> in deaerated MeCN containing 0.10 M Bu<sub>4</sub>NClO<sub>4</sub> was also observed upon addition of Sc(OTf)<sub>3</sub>, suggesting that the large positive shift of the one-electron reduction potential of PTIO<sup>•</sup> (equivalent to the one-electron oxidation potential of PTIO<sup>-</sup>) in the presence of Sc(OTf)<sub>3</sub> may result in the disproportionation. When H<sub>2</sub>O was added to the PTIO<sup>•</sup>-Sc(OTf)<sub>3</sub> system in deaerated MeCN, PTIO<sup>•</sup> was completely regenerated. It is suggested that the complex formation of Sc<sup>3+</sup> with H<sub>2</sub>O may weaken the interaction between PTIO<sup>-</sup> and Sc<sup>3+</sup>, leading to electron-transfer comproportionation to regenerate PTIO<sup>•</sup>. The reversible disproportionation of PTIO<sup>•</sup> was also confirmed by electron paramagnetic resonance (EPR) spectroscopy. Disproportionation ; Acetonitrile ; Chemistry ; Scandium ; Ion ; Electron transfer ; Oxide ; Photochemistry ; Inorganic chemistry ; Catalysis ; Organic chemistry Chemical Synthesis and Reactions ; Synthesis and Biological Evaluation ; Synthesis and biological activity
Authors: Elias Börjesson | Clemens V. Verhoosel | Joris J. C. Remmers | Martin Fagerström
Source: Finite Elements in Analysis and Design (article, 2024-09-26)
Field: Materials Science — Polymers and Plastics

Meso-scale modelling of complex fibre composite geometries using an immersed boundary method This paper investigates the application of immersed methods to simplify the discretisation and modelling process for meso-scale geometries in fibre-reinforced composites. The geometry of meso-scale structures in fibre-reinforced composites can often be categorised as complex, and frequently presents considerable challenges for meshing software. This complexity necessitates either time-consuming manual intervention or the adoption of simplified discretisation approaches, such as voxel methods, which may compromise accuracy. To address this issue, we study the use of immersed boundary methods, in combination with B-splines, for the discretisation of the matrix regions of the meso-scale geometry. This combination has the potential to minimise the requirement for manual intervention in the discretisation processes with little effect to the accuracy of e.g. stresses. We validate the proposed modelling framework in three numerical examples, where homogenised stiffnesses and stress levels are analysed in various fibre composite architectures. • Finite Cell Method for automatic discretisation of matrix regions in meso-scale fibre composites models. • Ghost penalty method for stabilisation and avoiding artificial stress peaks in results. • Homogenisation of membrane and bending stiffness in 3D woven composite with complex geometry. • Investigation on how transverse stresses in thin-ply woven composites are affected by different bundle thicknesses. Finite element method ; Composite number ; Scale (ratio) ; Boundary (topology) ; Structural engineering ; Materials science ; Mathematics ; Composite material ; Engineering ; Mathematical analysis ; Physics Textile materials and evaluations ; Computer Graphics and Visualization Techniques ; 3D Shape Modeling and Analysis
Authors: Yuxin Zhao | Yichi Zhang | Yong Huang
Source: Angewandte Chemie (article, 2024-06-12)
Field: Chemistry — Organic Chemistry

Enantioselective Relay Coupling of Perfluoroalkyl and Vinylogous Ketyl Radicals Abstract β‐Chiral carboxylic acids and their derivatives are highly valuable structural motifs in the fields of asymmetric synthesis and medicinal chemistry. However, the introduction of a sterically demanding sidechain to the β‐carbon, such as an all‐carbon quaternary center, remains a significant challenge in classical polar processes. Recently, N ‐heterocyclic carbene (NHC) mediated coupling reactions involving persistent ketyl radicals have emerged as a promising strategy to assemble highly crowded carbon‐carbon bonds. Nevertheless, achieving enantioselectivity in these reactions remains highly challenging. In this work, we report our recent progress in controlling enantioselectivity for relay coupling of perfluoroalkyl and persistent vinylogous ketyl radicals. We developed a chiral bifunctional NHC‐squaramide catalyst that achieves high facial selectivity in a critical bond‐forming event involving the coupling of a congested tertiary carbon radical and vinylogous ketyl radical. Chiral carboxylates bearing an all‐carbon quaternary center at the β‐position can be prepared in good yield and excellent enantiomeric excess. Results from density functional theory (DFT) calculations and nuclear Overhauser effect (NOE) experiments indicate that the N , N’ ‐diaryl squaramide motif adopts an unusual syn ‐ syn conformation, enabling hydrogen bonding interactions with the enolate oxygen, thereby rigidifying the overall conformation of the transition state. Ketyl ; Chemistry ; Radical ; Enantioselective synthesis ; Squaramide ; Carbene ; Steric effects ; Photochemistry ; Stereochemistry ; Organic chemistry ; Catalysis ; Organocatalysis Radical Photochemical Reactions ; Catalytic C–H Functionalization Methods ; Catalytic Cross-Coupling Reactions
Authors: Omar Dasser | Othman Filali Benaceur | Salma Fadel
Source: bioRxiv (Cold Spring Harbor Laboratory) (preprint, 2024-10-22)
Field: Materials Science — Materials Chemistry

Generative AI for Drug Discovery: A GPT-2 and LSTM Based Models for Designing EGFR Inhibitors Abstract The design of novel EGFR inhibitors is a critical focus in cancer drug discovery. This study leverages generative AI models, specifically fine-tuned GPT-2 and LSTM architectures, to generate new chemical structures targeting the Epidermal Growth Factor Receptor (EGFR). The models were trained on a curated dataset of approximately 500,000 bioactive ligands from the ChEMBL database, with SMILES strings as input. After generating a batch of 1,000 molecules, post-generation filtering was applied based on Lipinski’s rule of five, Quantitative Estimate of Drug-likeness (QED), and Synthetic Accessibility Scores (SAS) to ensure drug-like properties. Molecular docking studies were performed using PyRx with AutoDock Vina, focusing on the crystal structure of EGFR (PDB ID: 1M17). The LSTM model outperformed GPT-2, achieving a higher validity rate (90.98% vs. 52.27%) and similar uniqueness rates, while also producing molecules with stronger binding affinities, ranging from -9.4 to -10.4 kcal/mol. The results indicate that the LSTM model is more effective for generating chemically valid EGFR inhibitors, offering promising candidates for further experimental validation. This study demonstrates the potential of generative AI to accelerate the identification of effective cancer therapeutics. Generative grammar ; Drug discovery ; Computer science ; Drug ; Artificial intelligence ; Generative model ; Computational biology ; Machine learning ; Bioinformatics ; Pharmacology ; Biology Machine Learning in Materials Science ; Statistical and Computational Modeling
Authors: Barbora Šalovská | Wenxue Li | Oliver M. Bernhardt | Pierre‐Luc Germain | Tejas Gandhi | Lukas Reiter | Yansheng Liu
Source: bioRxiv (Cold Spring Harbor Laboratory) (preprint, 2024-10-31)
Field: Chemistry — Spectroscopy

A Comprehensive and Robust Multiplex-DIA Workflow Profiles Protein Turnover Regulations Associated with Cisplatin Resistance Measuring protein turnover is essential for understanding cellular biological processes and advancing drug discovery. The multiplex DIA mass spectrometry (DIA-MS) approach, combined with dynamic SILAC labeling (pulse-SILAC, or pSILAC), has proven to be a reliable method for analyzing protein turnover and degradation kinetics. Previous multiplex DIA-MS workflows have employed various strategies, including leveraging the highest isotopic labeling channels of peptides to enhance the detection of isotopic MS signal pairs or clusters. In this study, we introduce an improved and robust workflow that integrates a novel machine learning strategy and channel-specific statistical filtering, enabling dynamic adaptation to systematic or temporal variations in channel ratios. This allows comprehensive profiling of protein turnover throughout the pSILAC experiment without relying solely on the highest channel signals. Additionally, we developed <b><i>KdeggeR</i></b> , a data processing and analysis package optimized for pSILAC-DIA experiments, which estimates and visualizes peptide and protein degradation rates and dynamic profiles. Our integrative workflow was benchmarked on both 2-channel and 3-channel standard DIA datasets and across two mass spectrometry platforms, demonstrating its broad applicability. Finally, applying this workflow to an aneuploid cancer cell model before and after cisplatin resistance development demonstrated a strong negative correlation between transcript regulation and protein degradation for major protein complex subunits. We also identified specific protein turnover signatures associated with cisplatin resistance. Workflow ; Multiplex ; Cisplatin ; Resistance (ecology) ; Business ; Computer science ; Computational biology ; Bioinformatics ; Biology ; Medicine ; Internal medicine ; Database Advanced Proteomics Techniques and Applications ; Microbial Metabolic Engineering and Bioproduction ; Bioinformatics and Genomic Networks
Authors: Arantxa Forte‐Castro | Juana M. Pérez | Celia García-Mañas | Guillermo Garcia‐Garcia | Pedro Urquiza | Tania Romacho | Ignacio Fernández
Source: Sustainable Chemistry and Pharmacy (article, 2024-11-06)
Field: Chemistry — Organic Chemistry

New Copper(I) oxide biocatalyst based on functionalized olive stone for the synthesis of 1,4-disubstituted-1,2,3-triazoles under very mild conditions Copper ; Biocatalysis ; Chemistry ; Oxide ; Organic chemistry ; Combinatorial chemistry ; Catalysis ; Reaction mechanism Click Chemistry and Applications ; Synthesis and Characterization of Heterocyclic Compounds ; Synthesis and biological activity
Authors: Uzma Ghani | Fareeha Khalid Ghori | Muhammad Usman Qamar | Hina Khan | Basit Azad | Sabahat Habib | Saira Justin | Ishaq Khan | Tawaf Ali Shah | Gamal A. Shazly | Mohammed Bourhia | Fouzia Perveen | Aneela Javed
Source: Frontiers in Oncology (article, 2024-11-22)
Field: Materials Science — Biomaterials

SLNP-based CDK4- targeted nanotherapy against glioblastoma Our results indicated that Sil and SLNP-Sil are promising therapeutic approaches against glioblastoma and merit <i>in vivo</i> experimental verification using orthotropic xenograft mouse models against glioblastoma. U87 ; Viability assay ; Cancer research ; Chemistry ; Drug ; Glioblastoma ; IC50 ; Pharmacology ; Cell growth ; Cell culture ; In vitro ; Cell cycle ; Cytotoxicity ; Drug delivery ; Cell ; Medicine ; Biochemistry ; Biology Nanoparticle-Based Drug Delivery ; Retinoids in leukemia and cellular processes ; Cancer therapeutics and mechanisms
Authors: Zheng Zhao | Philip E. Bourne
Source: ChemRxiv (preprint, 2024-04-22)
Field: Chemistry — Organic Chemistry

Exploring Extended Warheads of Reversible and Irreversible Cysteine-Targeted Covalent Kinase Inhibitors In designing covalent kinase inhibitors (CKIs), the inclusion of electrophiles as attacking warheads demands careful choreography, ensuring not only their presence on the scaffold moiety but also their precise interaction with nucleophiles in the binding sites. Given the limited number of known electrophiles, exploring adjacent chemical space to broaden the palette of available electrophiles capable of covalent inhibition, is desirable. Here, we perform a systematic analysis of the characteristics of warheads and corresponding adjacent fragments for use in CKI design. We first collect all the released cysteine-targeted CKIs from multiple databases and create one CKI dataset containing 16,961 kinase-inhibitor data points from 12,381 unique CKIs covering 146 kinases with accessible cysteines in their binding pockets. Then we analyze this dataset, focusing on the extended warheads (i.e., warheads + adjacent fragments) — including 30 common warheads and 1344 unique adjacent fragments. Thus, we provide structural insights, and delineate chemical properties, and patterns in these extended warheads. Notably, we highlight the privileged patterns observed within reversible CKIs for the popular warheads cyanoacrylamide and aldehyde. This study provides medicinal chemists with novel insights into extended warheads and a comprehensive source of adjacent fragments, thus guiding the design, synthesis, and optimization of CKIs. Cysteine ; Covalent bond ; Chemistry ; Kinase ; Warhead ; Biochemistry ; Enzyme ; Engineering Click Chemistry and Applications ; Enzyme function and inhibition ; Protein Degradation and Inhibitors