Current Chemical Biology - Online First

Acute Myeloid Leukemia (AML) is characterized by uncontrolled proliferation of aberrant white blood cells, contributing to high morbidity and mortality rates, particularly among males. Targeting key enzymes involved in AML progression represents a promising therapeutic strategy.

This study applied computational drug discovery techniques to identify potential AML inhibitors targeting Tyrosine Kinase (TK), Protein Kinase C Beta (PKC), Myeloid Cell Leukemia 1 (MCL-1), and Histone Acetyltransferase (HAT). Inhibitors were retrieved from the ChEMBL database, molecular descriptors computed using PaDEL, and machine learning models evaluated via LazyPredict. QSAR modeling with a Random Forest Regressor achieved >90% accuracy in predicting pIC50 values. Lead compounds underwent molecular docking (PyRx), ADMET profiling (ADMETlab2.0), and molecular dynamics simulations (NMSim) to assess binding affinity, pharmacokinetics, and stability.

The QSAR model showed a strong correlation between predicted and experimental pIC50 values. Docking studies and ADMET analysis identified a novel compound with favorable pharmacokinetic properties and strong inhibitory potential. MD simulations confirmed stable binding conformations within target enzymes.

The integration of QSAR modeling, docking, and ADMET screening efficiently identified promising AML enzyme inhibitors, demonstrating the value of computational pipelines in early-stage drug discovery.

This study highlights a novel lead compound with potential as a multi-target AML therapeutic candidate, warranting further in vitro and in vivo validation.

The study investigates the quantification of sinensetin, a bioactive compound with antioxidant, anti-obesity, and anti-cancer properties, in cat's whiskers (Orthosiphon aristatus). The primary aim is to evaluate the effect of different extraction methods on sinensetin yield and to validate an high-performance liquid chromatography (HPLC) method for accurate quantification.

The research employed two extraction techniques: reflux and maceration. The HPLC method was validated for accuracy, precision, linearity, and specificity using a reverse-phase C18 column maintained at 25°C. The mobile phase consisted of acetonitrile (60:40) and 0.1% formic acid, with an isocratic elution. A 20 µl injection volume and a flow rate of 1 ml/min were used for analysis.

Validation results indicated a recovery rate of 98.37 ± 3.44% and a precision relative standard deviation (RSD) of 1.12%. The linearity correlation value was found to be 0.999. Sinensetin concentrations were quantified at 0.42 ± 0.006% for the macerated extract and 0.30 ± 0.006% for the reflux extract.

The findings demonstrate that the HPLC method is both accurate and precise for determining sinensetin levels, with maceration yielding higher concentrations than reflux. These results contribute to the understanding of extraction efficiency and the potential therapeutic applications of sinensetin.

This study confirms that accurate quantification of sinensetin in cat's whiskers is achievable using validated HPLC methods, highlighting the importance of extraction techniques in maximising bioactive compound yields.

The global rise in antibiotic resistance among pathogenic bacteria poses a critical threat to public health. Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, displays both intrinsic and acquired resistance mechanisms. Emerging evidence implicates post-transcriptional tRNA modifications in antibiotic resistance, positioning tRNA-modifying enzymes like trmA as potential therapeutic targets.

This study aims to identify potential inhibitors of trmA to disrupt essential cellular pro- cesses and counter antibiotic resistance.

We employed a structure-based virtual screening strategy to identify compounds structurally analogous to S-adenosylmethionine, a universal methyl group donor and known trmA binder. Top-ranked compounds were further evaluated through molecular dynamics (MD) simulations to examine binding-induced conformational dynamics and stability.

Compound 24762163 emerged as a lead candidate with favorable binding affinity and structural compatibility, as confirmed through docking and MD simulations. The compound formed stable interactions with the active site of trmA, indicating its inhibitory potential.

The computational findings suggest that compound 24762163 may effectively disrupt trmA function, thereby impairing tRNA methylation and hindering protein synthesis in P. aeruginosa. Given the essential role of tRNA modifications in bacterial survival and resistance, targeting trmA represents a promising strategy for novel antimicrobial development.

This study identifies compound 24762163 as a promising trmA inhibitor and a potential therapeutic agent to counter antibiotic resistance in Pseudomonas aeruginosa. Targeting tRNA-modifying methyltransferases may offer a novel approach in the fight against drug-resistant pathogens.

Scientific and non-scientific groups have contributed to raising awareness in recent years about animal welfare. The results of such efforts include the creation of legal frameworks concerning animal abuse (or mistreatment) and the growing number of technical requirements for the commercial exploitation of animal-derived products (such as beef, milk, and eggs). Nonetheless, thermal stress is poorly explored in animal welfare research despite its life-threatening consequences.

In this study, we discuss the biochemical and physiological effects of thermal stress in cattle, broilers, dogs and cats.

This review was conducted using data published in Portuguese and English, retrieved from Lilacs, Scielo, and PubMed databases, using the keywords “stress, cold, heat, canines, felines, broilers, poultry, milk cattle, and beef cattle”. Papers were considered if they were published from 2013 to 2025.

Thermal stress refers to a series of biochemical and physiological changes that occur due to short-, moderate-, or long-term exposure to excessively high or low temperatures, where adaptive mechanisms fail to restore normal body temperature. Defining ideal body temperatures for animals can be challenging, as they are influenced by factors such as sex, general health status, body mass, species, and breed. In the species studied, heat typically increases levels of Reactive Oxygen Species (ROS), cortisol, transaminases, creatine kinase, and lactic acid, while decreasing levels of Superoxide Dismutase (SOD) and ATP. Cold exposure increases T4 production, proinflammatory cytokines, such as TNF-α and IL-4, and decreases SOD and lipid content in various tissues.

Studies on thermal stress are necessary to provide evidence on what actions are needed to control and adjust environmental conditions for proper husbandry of production and companion animals.