This study reports the synthesis, characterization, and biological evaluation of a series of pyrazolyl–thiazole derivatives of thiophene. Seven compounds were synthesized and characterized using NMR spectroscopy and mass spectrometry. The antimicrobial activities of these derivatives were evaluated against various bacterial (Escherichia coli, Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus) and fungal strains (Aspergillus niger, Aspergillus oryzae, Rhizopus, Candida albicans), demonstrating significant inhibition zones and low minimum inhibitory concentrations (MIC). In addition, the compounds exhibited notable antioxidant activities in DPPH and hydroxyl radical scavenging assays. Computational studies, including density functional theory (DFT) calculations and molecular docking simulations, were performed to understand the electronic properties and binding interactions of the synthesized compounds with biological targets. The molecular docking results supported the experimental findings, highlighting the potential of these pyrazolyl–thiazole derivatives as multifunctional therapeutic agents with both antimicrobial and antioxidant properties.

Currently, there are several drugs used for the treatment of type 2 diabetes (T2D); however, all of them have adverse effects. Benzothiazoles have a broad spectrum of biological activities such as antidiabetic. This study aimed to evaluate in silico and in vivo two series of 2-aminobenzothiazole derivatives linked to isothioureas (3a–w) or guanidines (4a–z) for the treatment of T2D. The ADMET properties were determined in silico, from which it was possible to select nine compounds (two isothioureas and seven guanidines), and, with molecular docking, it was shown that compounds methyl (E)-N′-(benzo[d]thiazol-2-yl)-N-methylcarbamimidothioate (3b) and 2-(benzo[d]thiazol-2-yl)-1,3-di-tert-butylguanidine (4y) showed a high affinity for PPARγ (ΔG = −7.8 and −8.4 kcal/mol, respectively). In vivo, the LD50 value was estimated in rats based on OECD Guideline 425, being >1750 mg/kg for both compounds. The pharmacological effect of 3b and 4y was evaluated in the T2D rat model, showing that after oral administration in an equimolar ratio to pioglitazone (15 mg/kg) for 4 weeks, both compounds were able to reduce blood glucose levels (<200 mg/dL) and improve the lipid profile. Therefore, 3b and 4y could be used in the future as antidiabetic agents.

Thyroid hormone binds to specific nuclear receptors, regulating the expression of target genes, with major effects on cardiac function. Triiodothyronine (T3) increases the expression of key proteins related to calcium homeostasis, such as the sarcoplasmic reticulum calcium ATPase pump, but the detailed mechanism of gene regulation by T3 in cardiac voltage-gated calcium (Cav1.2) channels remains incompletely explored. Furthermore, the effects of T3 on Cav1.2 auxiliary subunits have not been investigated. We conducted quantitative reverse transcriptase polymerase chain reaction, Western blot, and immunofluorescence experiments in H9c2 cells derived from rat ventricular tissue, examining the effects of T3 on the expression of α1c, the principal subunit of Cav1.2 channels, and Cavβ4, an auxiliary Cav1.2 subunit that regulates gene expression. The translocation of phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB) by T3 was also examined. We found that T3 has opposite effects on these channel proteins, upregulating α1c and downregulating Cavβ4, and that it increases the nuclear translocation of pCREB while decreasing the translocation of Cavβ4. Finally, we found that overexpression of Cavβ4 represses the mRNA expression of α1c, suggesting that T3 upregulates the expression of the α1c subunit in response to a decrease in Cavβ4 subunit expression.

Curcumin and 5-bromoindole-3-carboxaldehyde were tested for their ability to inhibit quorum sensing-dependent virulence factors in Pseudomonas aeruginosa strains Pa01, Pa14, and ATCC 27853. The compounds were evaluated at curcumin (1 and 5 μg/mL) and 5-bromoindole-3-carboxaldehyde (30, 50, and 100 μg/mL). Virulence factors─exoprotease, elastase, pyocyanin, and alginate─were measured. Chemoinformatics properties were analyzed using Molinspiration, Molsoft, Osiris Property Explorer, pkCSM, and SwissADME. Results showed 5-bromoindole-3-carboxaldehyde significantly reduced pyocyanin in Pa01 (92.5% at 100 μg/mL), elastase (79.85% at 100 μg/mL), exoprotease (92.8% at 50 μg/mL), and alginate in ATCC 27853 (76.16% at 100 μg/mL). Curcumin effectively inhibited pyocyanin in ATCC 27853 (100% at 5 μg/mL), elastase in Pa14 (56.19% at 5 μg/mL), exoprotease in Pa01 (87.04% at 5 μg/mL), and alginate (48.26% at 5 μg/mL). Both compounds demonstrated strong inhibition of virulence factors, suggesting their potential as antivirulence agents against P. aeruginosa, a highly resistant bacterium prevalent in nosocomial infections.

Chagas disease is caused by the parasite Trypanosoma cruzi. One of the two first-line drugs for treatment is nifurtimox, a nitrofuran that exhibits high toxicity. Therefore, the need arises to investigate new therapeutic options, and, in this sense, our objective was to study compounds that maintain the trypanocidal activity associated with the furan nucleus and by structural modification of substituents reduce their toxicity. In the following research work, a chemical library was formed using the databases PubChem, ChEMBL and ChemSpider, later a virtual screening was carried out with the chemoinformatic tools Way2Drug, molinspiration, DataWarrior and admetSAR obtaining the prediction of biological activity, physicochemical parameters, data of toxicity and pharmacokinetic properties, respectively. The last stage consisted of the molecular docking of the molecules at the active site of the trypanothione reductase protein of Trypanosoma cruzi, determining its binding energy and intermolecular interactions. Compounds NF-85, NF-150, NF-246 and NF-279 with potential anti-T. cruzi activity were identified, the four molecules had greater affinity for trypanothione reductase (-7.0, -7.2, -7.0 and -7.3 kcal / mol, respectively), compared to nifurtimox (-6.7 kcal / mol).

Curcumin and 5-bromoindole-3-carboxaldehyde were tested for their ability to inhibit quorum sensing-dependent virulence factors in Pseudomonas aeruginosa strains Pa01, Pa14, and ATCC 27853. The compounds were evaluated at curcumin (1, 5 μg/ml) and 5-bromoindole-3-carboxaldehyde (30, 50, 100 μg/ml). Virulence factors—exoprotease, elastase, pyocyanin, and alginate —were measured. Chemoinformatics properties were analyzed using Molinspiration, Molsoft, Osiris Property Explorer, pkCSM, and SwissADME. Results showed 5-bromoindole-3-carboxaldehyde significantly reduced pyocyanin in Pa01 (92.5% at 100 μg/ml), elastase (79.85% at 100 μg/ml), exoprotease (92.8% at 50 μg/ml), and alginate in ATCC 27853 (76.16% at 100 μg/ml). Curcumin effectively inhibited pyocyanin in ATCC 27853 (100% at 5 μg/ml), elastase in Pa14 (56.19% at 5 μg/ml), exoprotease in Pa01 (87.04% at 5 μg/ml), and alginate (48.26% at 5 μg/ml). Both compounds demonstrated strong inhibition of virulence factors, suggesting their potential as anti-virulence agents against P. aeruginosa , a highly resistant bacterium prevalent in nosocomial infections.