Insights and perceptions: Investigating pregnant women's attitudes, understanding, and factors influencing knowledge regarding medication usage during pregnancy-A cross-sectional study.

Background: Medication use during pregnancy is a critical concern due to potential risks to both the mother and fetus. To the extent of our knowledge, there has been no prior research to assess medication use and identify the specific factors of pregnant women within the Yemeni community. This study aimed to investigate the knowledge, beliefs, and practices of Yemeni pregnant women regarding medication use and assess the factors associated with the knowledge during pregnancy.

Comprehensive Profiling of Roquin Binding Preferences for RNA Stem-Loops.

The cellular levels of mRNAs are controlled post-transcriptionally by cis-regulatory elements located in the 3'-untranslated region. These linear or structured elements are recognized by RNA-binding proteins (RBPs) to modulate mRNA stability. The Roquin-1 and -2 proteins specifically recognize RNA stem-loop motifs, the trinucleotide loop-containing constitutive decay elements (CDEs) and the hexanucleotide loop-containing alternative decay elements (ADEs), with their unique ROQ domain to initiate mRNA degradation.

In Vitro Evaluation of Antipseudomonal Activity and Safety Profile of Peptidomimetic Furin Inhibitors.

Inhibitors of the serine protease furin have been widely studied as antimicrobial agents due to their ability to block the cleavage and activation of certain viral surface proteins and bacterial toxins. In this study, the antipseudomonal effects and safety profiles of the furin inhibitors MI-1851 and MI-2415 were assessed. Fluorescence quenching studies suggested no relevant binding of the compounds to human serum albumin and α-acid glycoprotein.

Chem-CRISPR/dCas9FCPF: a platform for chemically induced epigenome editing.

Epigenetic aberration is one of the major driving factors in human cancer, often leading to acquired resistance to chemotherapies. Various small molecule epigenetic modulators have been reported. Nonetheless, outcomes from animal models and clinical trials have underscored the substantial setbacks attributed to pronounced on- and off-target toxicities.

Gibberellic Acid (GA): A Versatile Chiral Building Block for Syntheses of Pharmaceutical Agents.

Gibberellic acid (GA), an ent-kaurene tetracyclic diterpene, has been considered to be a chiral pool for the chemical transformation of significant heterocyclic compounds. This chiral pool continues to influence modern synthetic chemistry as an inexpensive and versatile starting material since it is widely applied in agriculture. This review focuses on the stereoselective syntheses of bioactive agents with pharmaceutical potency prepared from Gibberellic acid.

Synthesis of Tumor Selective Indole and 8-Hydroxyquinoline Skeleton Containing Di-, or Triarylmethanes with Improved Cytotoxic Activity.

The reaction between glycine-type aminonaphthol derivatives substituted with 2- or 1-naphthol and indole or 7-azaindole has been tested. Starting from 2-naphthol as a precursor, the reaction led to the formation of ring-closed products, while in the case of a 1-naphthol-type precursor, the desired biaryl ester was isolated. The synthesis of a bifunctional precursor starting from 5-chloro-8-hydroxyquinoline, morpholine, and ethyl glyoxylate via modified Mannich reaction is reported.

Strategic Fluorination to Achieve a Potent, Selective, Metabolically Stable, and Orally Bioavailable Inhibitor of CSNK2.

The host kinase casein kinase 2 (CSNK2) has been proposed to be an antiviral target against β-coronaviral infection. To pharmacologically validate CSNK2 as a drug target in vivo, potent and selective CSNK2 inhibitors with good pharmacokinetic properties are required. Inhibitors based on the pyrazolo[1,5-]pyrimidine scaffold possess outstanding potency and selectivity for CSNK2, but bioavailability and metabolic stability are often challenging.

The future of pharmacology and therapeutics of the arachidonic acid cascade in the next decade: Innovative advancements in drug repurposing.

Many drugs can act on multiple targets or disease pathways, regardless of their original purpose. Drug repurposing involves reevaluating existing compounds for new medical uses. This can include repositioning approved drugs, redeveloping unapproved drugs, or repurposing any chemical, nutraceutical, or biotherapeutic product for new applications.

Automated design of multi-target ligands by generative deep learning.

Generative deep learning models enable data-driven de novo design of molecules with tailored features. Chemical language models (CLM) trained on string representations of molecules such as SMILES have been successfully employed to design new chemical entities with experimentally confirmed activity on intended targets. Here, we probe the application of CLM to generate multi-target ligands for designed polypharmacology.

Nucleocapsids of the Rift Valley fever virus ambisense S segment contain an exposed RNA element in the center that overlaps with the intergenic region.

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen. Its RNA genome consists of two negative-sense segments (L and M) with one gene each, and one ambisense segment (S) with two opposing genes separated by the noncoding "intergenic region" (IGR). These vRNAs and the complementary cRNAs are encapsidated by nucleoprotein (N).

Macrocyclic Inhibitors Targeting the Prime Site of the Fibrinolytic Serine Protease Plasmin.

Two series of macrocyclic inhibitors addressing the S1 pocket and the prime site of the fibrinolytic serine protease plasmin have been developed. In the first series, a P1 tranexamoyl residue was coupled to 4-aminophenylalanine in P1' position, which provided moderately potent inhibitors with inhibition constants around 1 μM. In the second series, a substituted biphenylalanine was incorporated as P1' residue leading to approximately 1000-fold stronger plasmin inhibitors, the best compounds possess subnanomolar inhibition constants.

Thermodynamic Characterization of LC3/GABARAP:Ligand Interactions by Isothermal Titration Calorimetry.

Isothermal titration calorimetry (ITC) is a widely used technique for the characterization of protein-protein and protein-ligand interactions. It provides information on the stoichiometry, affinity, and thermodynamic driving forces of interactions. This chapter exemplifies the use of ITC to investigate interactions between human autophagy modifiers (LC3/GABARAP proteins) and their interaction partners, the LIR motif-containing sequences.

High-Throughput Screening for LC3/GABARAP Binders Utilizing the Fluorescence Polarization Assay.

The characterization of interactions between autophagy modifiers (Atg8-family proteins) and their natural ligands (peptides and proteins) or small molecules is important for a detailed understanding of selective autophagy mechanisms and for the design of potential Atg8 inhibitors that affect the autophagy processes in cells. The fluorescence polarization (FP) assay is a rapid, cost-effective, and robust method that provides affinity and selectivity information for small molecules and peptide ligands targeting human Atg8 proteins.This chapter introduces the basic principles of FP assays.

Development of a Crystallographic Screening to Identify Sudan Virus VP40 Ligands.

The matrix protein VP40 of the highly pathogenic Sudan virus (genus ) is a multifunctional protein responsible for the recruitment of viral nucleocapsids to the plasma membrane and the budding of infectious virions. In addition to its role in assembly, VP40 also downregulates viral genome replication and transcription. VP40's existence in various homo-oligomeric states is presumed to underpin its diverse functional capabilities during the viral life cycle.

Synthesis and evaluation of chemical linchpins for highly selective CK2α targeting.

Casein kinase-2 (CK2) are serine/threonine kinases with dual co-factor (ATP and GTP) specificity, that are involved in the regulation of a wide variety of cellular functions. Small molecules targeting CK2 have been described in the literature targeting different binding pockets of the kinase with a focus on type I inhibitors such as the recently published chemical probe SGC-CK2-1. In this study, we investigated whether known allosteric inhibitors binding to a pocket adjacent to helix αD could be combined with ATP mimetic moieties defining a novel class of ATP competitive compounds with a unique binding mode.

()-2-Benzylidenecyclanones: Part XIX. Reaction of ()-2-(4'-X-Benzylidene)-1-tetralones with Cellular Thiols: Comparison of Thiol Reactivities of Open-Chain Chalcones and Their Six- and Seven-Membered Cyclic Analogs.

Non-enzyme-catalyzed thiol addition onto the α,β-unsaturated carbonyl system is associated with several biological effects. Kinetics and diastereoselectivity of non-enzyme catalyzed nucleophilic addition of reduced glutathione (GSH) and N-acetylcysteine (NAC) to the six-membered cyclic chalcone analogs and were investigated at different pH values (pH 3.2, 7.

HTRF-based assay for detection of mono-ADP-ribosyl hydrolyzing macrodomains and inhibitor screening.

The COVID-19 pandemic has highlighted the lack of effective, ready-to-use antivirals for the treatment of viruses with pandemic potential. The development of a diverse drug portfolio is therefore crucial for pandemic preparedness. Viral macrodomains are attractive therapeutic targets as they are suggested to play an important role in evading the innate host immune response, making them critical for viral pathogenesis.

Potent anti-coronaviral activity of pateamines and new insights into their mode of action.

Pateamines, derived from the sponge , function as inhibitors of the RNA helicase eIF4A and exhibit promising antiviral and anticancer properties. eIF4A plays a pivotal role in unwinding stable RNA structures within the 5'-UTR of selected mRNAs, facilitating the binding of the 43S preinitiation complex during translation initiation. Pateamines function by clamping RNA substrates onto the eIF4A surface, effectively preventing eIF4A from carrying out the unwinding step.