The wide tissue distribution of the adrenergic β3 receptor makes it a potential target for the treatment of multiple pathologies such as diabetes, obesity, depression, overactive bladder (OAB), and cancer. Currently, there is only one drug on the market, mirabegron, approved for the treatment of OAB. In the present study, we have carried out an extensive structure-activity relationship analysis of a series of 41 aryloxypropanolamine compounds based on three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques. This is the first combined comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) study in a series of selective aryloxypropanolamines displaying anti-diabetes and anti-obesity pharmacological profiles. The best CoMFA and CoMSIA models presented values of r²_ncv = 0.993 and 0.984 and values of r²_test = 0.865 and 0.918, respectively. The results obtained were subjected to extensive external validation (q², r², r²_m, etc.) and a final series of compounds was designed and their biological activity was predicted (best pEC₅₀ = 8.561).

There is an urgent need for the development of new antibiotics. Here, we describe the inhibitory activity of new quinone compounds against methicillin-resistant Staphylococcus aureus (ATCC^® 43300), methicillin-sensitive S. aureus (ATCC^® 29213), and two clinical isolates from Chile (ISP-213 and ISP-214). We observed 99.9% reduction in viability within 2 h of exposure without the cultures exhibiting any post-antibiotic effect, which was twice the kinetics to that observed with vancomycin. These clinical isolates did not acquire resistance to these quinone derivatives during the course of our study. We found that these compounds protected larvae of the greater wax moth, sp. Galleria mellonella, from infection by these MRSA clinical strains as effectively as vancomycin. These quinone derivatives are potential drug candidates worth further development.

A rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC^® strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1–32 μg/mL against Gram-positive ATCC^® strains. The structure–activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16, were the MIC_50/90 were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC_50/90 was 256/512 µg/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.

The demand for sustainable methods to extract bioactive compounds from native fruits is increasing. We evaluated the potential of natural deep eutectic solvents (NaDES) combined with ultrasound-assisted extraction (UAE) to recover phenolic compounds from Ugni molinae Turcz. (murta), a Chilean fruit with recognized ethnopharmacological and antioxidant value. Seven choline chloride-based NaDESs (M1–M7) were assessed and compared with conventional methanol: formic acid extraction (M8). The choline chloride: 1,2-propanediol system (1:2, M2) achieved the highest recovery of total phenolics (64.87 mg GAE/g) and flavonoids (35.38 mg QE/g), together with strong antioxidant activity (DPPH IC₅₀: 1.05 µg/mL; ORAC: 40,291 µmol TE/g). When comparing the different NaDES formulations (M1–M8), M8 displayed superior FRAP and ORAC values, although its phenolic and flavonoid yields were lower, reflecting differences in solvent selectivity. HPLC-DAD analysis further revealed that NaDES, particularly M5 (choline chloride: oxalic acid, 1:1), favored the extraction of flavonoid and anthocyanin-type compounds. Multivariate and PCA analyses showed distinct chemical profiles in NaDES extracts, forming two clusters apart from M8. Pearson correlation analysis linked antioxidant capacity with major flavonoids. Overall, NaDES combined with UAE represents an efficient, green strategy for selectively recovering bioactives, supporting applications in foods, nutraceuticals, and health products from Chilean native fruits.

Background/Objectives: Hospital wastewater is a complex effluent containing a wide range of biological and chemical contaminants, including pharmaceuticals, pathogens, and antimicrobial resistance determinants. These discharges pose a growing threat to aquatic ecosystems and public health, particularly in regions where wastewater treatment is insufficient. This study aimed to characterize the chemical and microbiological composition of untreated effluent from a tertiary care hospital in southern Chile, focusing on contaminants of emerging concern. Methods: Wastewater samples were collected at the hospital outlet before any treatment. The presence of two commonly used pharmaceutical compounds, paracetamol and amoxicillin, was quantified using high-performance liquid chromatography (HPLC). Bacterial isolation was performed using selective media, and antibiotic susceptibility testing was conducted via the disk diffusion method following CLSI guidelines. In addition, metagenomic DNA was extracted and sequenced to assess microbial community composition and functional gene content, focusing on the identification of resistance genes and potential pathogens. Results: A total of 42 bacterial isolates were recovered, including genera with known pathogenic potential such as Aeromonas, Klebsiella, and Enterococcus. Antibiotic susceptibility tests revealed a high prevalence of multidrug-resistant strains. Metagenomic analysis identified the dominance of Bacillota and Bacteroidota, together with 56 antimicrobial-resistance gene (ARG) families and 38 virulence-factor families. Functional gene analysis indicated the presence of efflux-pump systems, β-lactamases, and mobile genetic elements, suggesting that untreated hospital effluents serve as potential sources of resistance and virulence determinants entering the environment. Paracetamol was detected in all samples, with an average concentration of 277.4 ± 10.7 µg/L; amoxicillin was not detected, likely due to its instability and rapid degradation in the wastewater matrix. Conclusions: These findings highlight the complex microbiological and chemical burden of untreated hospital wastewater and reinforce the need for continuous monitoring and improved treatment strategies to mitigate environmental dissemination of antibiotic resistance.

Resistance to antibacterial agents is a growing global public health problem that reduces the efficacy of available antibacterial agents, leading to increased patient mortality and morbidity. Unfortunately, only 16 antibacterial drugs have been approved by the FDA in the last 10 years, so it is necessary to develop new agents with novel chemical structures and/or mechanisms of action. In response to this, our group takes up the challenge of designing a new family of pyrimidoisoquinolinquinones displaying antimicrobial activities against multidrug-resistant Gram-positive bacteria. Accordingly, the objective of this study was to establish the necessary structural requirements to obtain compounds with high antibacterial activity, along with the parameters controlling antibacterial activity. To achieve this goal, we designed a family of compounds using different strategies for drug design. Forty structural candidates were synthesized and characterized, and antibacterial assays were carried out against high-priority bacterial pathogens. A variety of structural properties were modified, such as hydrophobicity and chain length of functional groups attached to specific carbon positions of the quinone core. All the synthesized compounds inhibited Gram-positive pathogens in concentrations ranging from 0.5 to 64 µg/mL. Two derivatives exhibited minimum inhibitory concentrations of 64 µg/mL against Klebsiella pneumoniae, while compound 28 demonstrated higher potency against MRSA than vancomycin.