The emergence of drug-resistant Staphylococcus aureus is responsible for high morbidity and mortality worldwide. New therapeutic options are needed to fight the increasing antimicrobial resistance among S. aureus in the clinical setting. We, therefore, characterized the in silico absorption, distribution, metabolism, elimination, and toxicity (ADMET) and in vitro antimicrobial activity of 5-nitro-2-thiophenecarbaldehyde N-((E)-(5-nitrothienyl)methylidene)hydrazone (KTU-286) against drug-resistant S. aureus strains with genetically defined resistance mechanisms. The antimicrobial activity of KTU-286 was determined by CLSI recommendations. The ADMET properties were estimated by using in silico modeling. The activity on biofilm integrity was examined by crystal violet assay. KTU-286 demonstrated low estimated toxicity and low skin permeability. The highest antimicrobial activity was observed among pan-susceptible (Pan-S) S. aureus (minimal inhibitory concentration (MIC) 0.5–2.0 µg/mL, IC₅₀ = 0.460 µg/mL), followed by vancomycin resistant S. aureus (VRSA) (MIC 4.0 µg/mL, IC₅₀ = 1.697 µg/mL) and methicillin-resistant S. aureus (MRSA) (MIC 1.0–16.0 µg/mL, IC₅₀ = 2.282 µg/mL). KTU-286 resulted in significant (p < 0.05) loss of S. aureus biofilm integrity in vitro. Further studies are needed for a better understanding of safety, synergistic relationship, and therapeutic potency of KTU-286.

Infections caused by multidrug-resistant bacterial and fungal pathogens represent a significant global health concern, contributing to increased morbidity and mortality rates. Therefore, it is crucial to develop novel compounds targeting drug-resistant microbial strains. Herein, we report the synthesis of amino acid derivatives bearing an incorporated 4-hydroxyphenyl moiety with various substitutions. The resultant novel 3-((4-hydroxyphenyl)amino)propanoic acid derivatives 2–37 exhibited structure-dependent antimicrobial activity against both ESKAPE group bacteria and drug-resistant Candida species. Furthermore, these derivatives demonstrated substantial activity against Candida auris, with minimum inhibitory concentrations ranging from 0.5 to 64 µg/mL. Hydrazones 14–16, containing heterocyclic substituents, showed the most potent and broad-spectrum antimicrobial activity. This activity extended to methicillin-resistant Staphylococcus aureus (MRSA) with MIC values ranging from 1 to 8 µg/mL, vancomycin-resistant Enterococcus faecalis (0.5–2 µg/mL), Gram-negative pathogens (MIC 8–64 µg/mL), and drug-resistant Candida species (MIC 8–64 µg/mL), including Candida auris. Collectively, these findings underscore the potential utility of the novel 3-((4-hydroxyphenyl)amino)propanoic acid scaffold for further development as a foundational platform for novel antimicrobial agents targeting emerging and drug-resistant bacterial and fungal pathogens.

Various cancer-associated morbidities remain a growing global health challenge, resulting in a significant burden on healthcare systems worldwide due to high mortality rates and a frequent lack of novel therapeutic options for advanced and localized disease. Reactive oxygen species (ROS) play an important role in cancer pathogenesis and response to chemotherapeutics; therefore, it is crucial to develop novel compounds with both antioxidant and anticancer activity. In this study, a series of previously reported 3-((4-hydroxyphenyl)amino)propanoic acid derivatives (compounds 1–36) were evaluated for their anticancer and antioxidant activities. Compounds 12, 20–22, and 29 were able to reduce A549 cell viability by 50% and suppress A549 cell migration in vitro. These compounds also showed favorable cytotoxicity properties towards noncancerous Vero cells. The most promising candidate, compound 20, exhibited potent antioxidant properties in the DPPH radical scavenging assay. These results demonstrate that 3-((4-hydroxyphenyl)amino)propanoic acid could be further explored as an attractive scaffold for the development of novel anticancer and antioxidant candidates.

Mitochondrial dysfunction during ischemic stroke ultimately manifests as ATP depletion. Mitochondrial ATP synthase upon loss of mitochondrial membrane potential during ischemia rapidly hydrolyses ATP and thus contributes to ATP depletion. Increasing evidence suggests that inhibition of ATP synthase limits ATP depletion and is protective against ischemic tissue damage. Bedaquiline (BDQ) is an anti-microbial agent, approved for clinical use, that inhibits ATP synthase of Mycobacteria; however recently it has been shown to act on mitochondrial ATP synthase, inhibiting both ATP synthesis and hydrolysis in low micromolar concentrations. In this study, we investigated whether preconditioning with BDQ can alleviate ischemia/reperfusion-induced brain injury in Wistar rats after middle cerebral artery occlusion-reperfusion and whether it affects mitochondrial functions. We found that BDQ was effective in limiting necrosis and neurological dysfunction during ischemia-reperfusion. BDQ also caused inhibition of ATPase activity, mild uncoupling of respiration, and stimulated mitochondrial respiration both in healthy and ischemic mitochondria. Mitochondrial calcium retention capacity was unaffected by BDQ preconditioning. We concluded that BDQ has neuroprotective properties associated with its action on mitochondrial respiration and ATPase activity.

Bovine colostrum (COL), the first milk secreted by lactating cows postpartum, is a rich source of bioactive compounds that exert a significant role in the survival, growth, and immune development of neonatal calves. This study investigated the immunomodulatory effects of COL on cytokine production in vitro using a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA). COL pretreatment significantly reduced IL-6 (241.3 pg/mL) production induced by PMA (p < 0.05), while increasing IL-10 production (45.3 pg/mL), in comparison to PMA control (441.1 and 12.5 pg/mL, respectively). Further investigations revealed that the IL-6 suppressive effect of colostrum was heat-sensitive and associated with components of higher molecular mass (100 kDa). Moreover, colostrum primarily influenced THP-1 macrophages rather than Caco-2 epithelial cells. The effects of colostrum on IL-6 production were associated with reduced NF-κB activation in THP-1 macrophages. In calf-FMT transplanted C57BL/6 murine model, colostrum decreased intestinal permeability, reduced immune cell infiltration and intestinal score, and suppressed IL-6 (142.0 pg/mL) production during S. typhimurium infection, in comparison to control animals (215.2 pg/mL). These results suggest the immunomodulatory activity of bovine colostrum and its potential applications in inflammatory disorders. Further studies are needed to elucidate the underlying mechanisms and validate the findings in bovine models.