Anna K. H. Hirsch
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View article: The One‐Step Synthesis of Biologically Active Isochromans from Lignin‐Derived Aromatic Monomers in Tunable Deep Eutectic Solvents
The One‐Step Synthesis of Biologically Active Isochromans from Lignin‐Derived Aromatic Monomers in Tunable Deep Eutectic Solvents Open
Clean synthetic strategies that embrace the inherent structural features of renewable building blocks to obtain biologically active compounds hold great potential to improve the economic viability of emerging biorefineries. Importantly, su…
View article: Design, Synthesis, and Biological Evaluation of Mono- and Diamino-Substituted Squaramide Derivatives as Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthase
Design, Synthesis, and Biological Evaluation of Mono- and Diamino-Substituted Squaramide Derivatives as Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthase Open
Amides of squaric acid are new drug candidates with activity against mycobacteria. Like the approved drug bedaquiline, these compounds achieve efficacy by inhibiting mycobacterial ATP synthase. However, squaramides have a different binding…
View article: Ein neuer Malariawirkstoff hemmt die Proteinsynthese von <i>Plasmodium falciparum</i>
Ein neuer Malariawirkstoff hemmt die Proteinsynthese von <i>Plasmodium falciparum</i> Open
Zusammenfassung Die auftretenden Resistenzen gegenüber fast allen Klassen von Malariawirkstoffen erfordern, dass die Entwicklungspipeline von Malariamitteln dringlich mit neuen Chemotypen mit neuen Wirkmechanismen gefüllt werden muss. Wir …
View article: A Novel Antimalarial Agent that Inhibits Protein Synthesis in <i>Plasmodium falciparum</i>
A Novel Antimalarial Agent that Inhibits Protein Synthesis in <i>Plasmodium falciparum</i> Open
The emergence of drug resistance to nearly all antimalarials following their rollout underscores the need for novel chemotypes with novel modes of action to replenish the antimalarial drug‐development pipeline. We identified a novel class …
View article: Tracheal tuft cell-released leukotrienes promote antibacterial immune responses
Tracheal tuft cell-released leukotrienes promote antibacterial immune responses Open
SUMMARY Tuft cells act as crucial sentinels in the airways that detect bacterial metabolites. In response, tuft cells release signaling molecules that trigger immune responses essential for clearing the infection. The molecular mechanisms …
View article: Targeting isoprenoid-precursor biosynthesis in Klebsiella pneumoniae: Design, synthesis and evaluation of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) inhibitors
Targeting isoprenoid-precursor biosynthesis in Klebsiella pneumoniae: Design, synthesis and evaluation of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) inhibitors Open
Klebsiella pneumoniae is a critical-priority pathogen based on the 2024 WHO list and poses a significant threat to human health. The methylerythritol phosphate (MEP) pathway, crucial for isoprenoid biosynthesis in many pathogenic bacteria,…
View article: Innovative zinc-binding inhibitors of Legionella pneumophila ProA reduce collagen and flagellin degradation, TLR5 evasion, and human lung tissue inflammation
Innovative zinc-binding inhibitors of Legionella pneumophila ProA reduce collagen and flagellin degradation, TLR5 evasion, and human lung tissue inflammation Open
Legionnaires' disease is a severe pneumonia caused by the aquatic bacterium Legionella pneumophila. In recent years, the number of cases has continuously increased according to the distribution of aerosol-producing technologies, global war…
View article: Engineering an Artificial Myxopyronin Derivative with Enhanced Metabolic Stability via Mutasynthesis
Engineering an Artificial Myxopyronin Derivative with Enhanced Metabolic Stability via Mutasynthesis Open
The rise of multidrug-resistant pathogens, such as Staphylococcus aureus and Mycobacterium tuberculosis, underscores an urgent need for therapeutic innovation. The antibiotic development pipeline targeting these bacteria is critically limi…
View article: Tobramycin crosslinking improves the colloidal stability of arginine chitosan biodynamers for safe and efficient siRNA delivery
Tobramycin crosslinking improves the colloidal stability of arginine chitosan biodynamers for safe and efficient siRNA delivery Open
We previously reported proteoid biodynamers to form dynamic nanocomplexes (dynaplexes, DPs) with siRNA and their efficient transfection via dynamic responsive changes in endosomal environments. However, their limited colloidal stability re…
View article: Domain adaptable language modeling of chemical compounds identifies potent pathoblockers for Pseudomonas aeruginosa
Domain adaptable language modeling of chemical compounds identifies potent pathoblockers for Pseudomonas aeruginosa Open
Computational techniques for predicting molecular properties are emerging as key components for streamlining drug development, optimizing time and financial investments. Here, we introduce ChemLM, a transformer language model for this task…
View article: Domain adaptable language modeling of chemical compounds identifies potent pathoblockers for Pseudomonas aeruginosa.
Domain adaptable language modeling of chemical compounds identifies potent pathoblockers for Pseudomonas aeruginosa. Open
Computational techniques for predicting molecular properties are emerging as pivotal components for streamlining drug development, optimizing time, and financial investments. Here, we introduce ChemLM, a transformer language model-based ap…
View article: Positive Charge in an Antimalarial Compound Unlocks Broad-Spectrum Antibacterial Activity
Positive Charge in an Antimalarial Compound Unlocks Broad-Spectrum Antibacterial Activity Open
In this study, we synthesized a library of eNTRy-rule-compliant compounds by introducing ionizable nitrogen atoms to an antimalarial compound. These positively charged derivatives gained activity against both Gram-negative and -positive ba…
View article: Dipeptidic Phosphonates: Potent Inhibitors of <i>Pseudomonas aeruginosa</i> Elastase B Showing Efficacy in a Murine Keratitis Model
Dipeptidic Phosphonates: Potent Inhibitors of <i>Pseudomonas aeruginosa</i> Elastase B Showing Efficacy in a Murine Keratitis Model Open
The ubiquitous opportunistic pathogen Pseudomonas aeruginosa is responsible for severe infections and notoriously known for acquiring antimicrobial resistance. Inhibiting the bacterium's extracellular elastase, LasB – a zinc‐dependent prot…
View article: From Dyrk1A inhibitors to a novel class of antiviral agents: Targeting Enterovirus EV-A71 with 2-aryl-substituted thiophene scaffolds
From Dyrk1A inhibitors to a novel class of antiviral agents: Targeting Enterovirus EV-A71 with 2-aryl-substituted thiophene scaffolds Open
Enterovirus A71 (EV-A71) is a major causative agent of hand, foot, and mouth disease (HFMD) especially in children. The majority of EV-A71 cases are mild, however, severe cases have exhibited an array of neurological complications which of…
View article: Unlocking the antiviral arsenal: Structure-guided optimization of small-molecule inhibitors against RSV and hCoV-229E
Unlocking the antiviral arsenal: Structure-guided optimization of small-molecule inhibitors against RSV and hCoV-229E Open
Acute respiratory diseases in humans can be caused by various viral pathogens such as respiratory syncytial virus (RSV), human coronavirus 229E (hCoV-229E), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To prevent sever…
View article: Targeting IspD for Anti-infective and Herbicide Development: Exploring Its Role, Mechanism, and Structural Insights
Targeting IspD for Anti-infective and Herbicide Development: Exploring Its Role, Mechanism, and Structural Insights Open
Antimicrobial resistance (AMR) and herbicide resistance pose threats to society, necessitating novel anti-infectives and herbicides exploiting untapped modes of action like inhibition of IspD, the third enzyme in the MEP pathway. The MEP p…
View article: Lignin-derived guaiacols as platform chemicals for the modular synthesis of 1,2,3,4-tetrahydroquinolines and benzomorpholines
Lignin-derived guaiacols as platform chemicals for the modular synthesis of 1,2,3,4-tetrahydroquinolines and benzomorpholines Open
The development of novel catalytic pathways for converting lignin-derived guaiacols, into biologically active 1,2,3,4-tetrahydroquinolines and benzomorpholines by applying hydrogen borrowing amination and C–N cross coupling as key catalyti…
View article: Tailored phenyl ureas eradicate drug-resistant <i>Mycobacterium tuberculosis</i> by targeting mycolic acid cell wall assembly
Tailored phenyl ureas eradicate drug-resistant <i>Mycobacterium tuberculosis</i> by targeting mycolic acid cell wall assembly Open
Treatment of Mycobacterium tuberculosis infections is a challenging task due to long treatment regiments and a growing number of resistant clinical isolates.
View article: Modular synthetic routes to biologically active indoles from lignin
Modular synthetic routes to biologically active indoles from lignin Open
Modular functionalization of a lignin-derived C2-acetal enables the synthesis of bio-based indoles via the formation of ortho -amino acetal derivatives and the in situ Schiff-base formation/intramolecular cyclization under mild reaction co…
View article: Fragment Discovery by X‐Ray Crystallographic Screening Targeting the CTP Binding Site of <i>Pseudomonas Aeruginosa</i> IspD
Fragment Discovery by X‐Ray Crystallographic Screening Targeting the CTP Binding Site of <i>Pseudomonas Aeruginosa</i> IspD Open
With antimicrobial resistance (AMR) reaching alarming levels, new anti‐infectives with unprecedented mechanisms of action are urgently needed. The 2‐ C ‐methylerythritol‐D‐erythritol‐4‐phosphate (MEP) pathway represents an attractive sourc…
View article: Dynamic Combinatorial Chemistry Unveils Nsp10 Inhibitors with Antiviral Potential Against SARS‐CoV‐2
Dynamic Combinatorial Chemistry Unveils Nsp10 Inhibitors with Antiviral Potential Against SARS‐CoV‐2 Open
The development of antiviral drugs against the Severe Acute Respiratory Syndrome coronavirus 2 (SARS‐CoV‐2) responsible for the recent Covid‐19 pandemic is crucial, as treatment options remain limited and vaccination does not prevent (re)i…
View article: Integral Solvent-Induced Protein Precipitation for Target-Engagement Studies in <i>Plasmodium falciparum</i>
Integral Solvent-Induced Protein Precipitation for Target-Engagement Studies in <i>Plasmodium falciparum</i> Open
The limited understanding of the mechanism of action (MoA) of several antimalarials and the rise of drug resistance toward existing malaria therapies emphasizes the need for new strategies to uncover the molecular target of compounds in Pl…
View article: Studying Target–Engagement of Anti-Infectives by Solvent-Induced Protein Precipitation and Quantitative Mass Spectrometry
Studying Target–Engagement of Anti-Infectives by Solvent-Induced Protein Precipitation and Quantitative Mass Spectrometry Open
Antimicrobial resistance (AMR) poses a serious threat to global health. The rapid emergence of resistance contrasts with the slow pace of antimicrobial development, emphasizing the urgent need for innovative drug discovery approaches. This…
View article: IspE kinase as an anti-infective target: Role of a hydrophobic pocket in inhibitor binding
IspE kinase as an anti-infective target: Role of a hydrophobic pocket in inhibitor binding Open
Enzymes of the methylerythritol phosphate (MEP) pathway are potential targets for antimicrobial drug discovery. Here, we focus on 4-diphosphocytidyl-2-C-methyl-D-erythritol (IspE) kinase from the MEP pathway. We use biochemical and structu…