Imidazole derivatives are considered potential chemical compounds that could be therapeutically effective against several harmful pathogenic microbes. The chemical structure of imidazole, with a five-membered heterocycle, three carbon atoms, and two double bonds, tends to show antibacterial activities. In the present study, novel imidazole derivatives were designed and synthesized to be evaluated as antimicrobial agents owing to the low number of attempts to discover new antimicrobial agents and the emerging cases of antimicrobial resistance. Two imidazole compounds were prepared and evaluated as promising candidates regarding in vitro cytotoxicity against human skin fibroblast cells and antimicrobial activity against several bacterial strains. The synthesized imidazole derivatives were chemically identified using nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR). The results demonstrated a relatively high cell viability of one of the imidazole derivatives, i.e., HL2, upon 24 and 48 h cell exposure. Both derivatives were able to inhibit the growth of the tested bacterial strains. This study provides valuable insight into the potential application of imidazole derivatives for treating microbial infections; however, further in vitro and in vivo studies are required to confirm their safety and effectiveness.

Heterocyclic compounds have shown that they hold significant therapeutic activities, highlighting the importance of discovering and developing novel candidates against cancers, infections, and oxidative stress-associated disorders. In this study, we demonstrated the biological activity of our previously synthesized thiazolidinone derivatives (TZDs-1, 6, and 7). Furthermore, we synthesized and structurally characterized a new derivative (TZD-5) using IR, ¹H NMR, and ¹³C NMR spectroscopy, confirming the presence of its key functional groups, namely, carbonyl and imine. Their antioxidant activity was assessed through the DPPH assay, with TZD-5 showing the most potent effect (IC₅₀ = 24.4 µg/mL), comparable to ascorbic acid, an effect attributed to the methoxy group introduced via N-alkylation. Cytotoxicity was evaluated using the MTS assay on normal (HFF-1) and cancerous (HepG2 and A549) cell lines at two time points: 24- and 48 h exposure. Our findings highlight clear differences in cytotoxicity and selectivity among the tested thiazolidinone derivatives. TZD-1 and TZD-6 demonstrated significant, dose-dependent cytotoxic effects on both cancerous (HepG2 and A549) and normal (HFF-1) cell lines, thus limiting their therapeutic potential due to insufficient selectivity. TZD-5 exhibited moderate selectivity with higher susceptibility for HepG2 cells compared to normal cells. Notably, TZD-7 showed the most favorable cytotoxic profile, demonstrating strong selective cytotoxicity toward cancer cell lines with minimal adverse effects on normal fibroblasts. Overall, the results highlight TZD-5 and TZD-7 as promising candidates for antioxidant and selective anticancer therapies.

Background/Objectives: Skin wounds interrupt the natural anatomy and function of the skin. The body passes through four physiological phases to repair wounds after injury. Since the fibers are more closely related to the extracellular matrix structure, they can be used as scaffolds to accelerate wound closure. Shikonin is a botanical herbal remedy used as an anti-inflammatory agent and for its wound-healing characteristics. Cresols are known for their bactericidal and fungicidal properties, which promote their utilization as a disinfectant in soap. Therefore, this study aimed to formulate shikonin and cresol-loaded nanofibers for a dual wound-healing and antibacterial wound dressing in vitro. Methods: This study demonstrated the effectiveness of the drug-loaded nanofibers against diverse Gram-positive and Gram-negative bacteria using the minimum inhibitory concentration (MIC) and zone of inhibition assays. Results: Scanning electron microscopy images showed successful formulation of shikonin/cresol fibers with an average diameter of 772 ± 152 nm. The encapsulation efficiency and drug loading for the dual drug-loaded fibers were 44 ± 1% and 25 ± 1 µg/mg, respectively, for shikonin, and 38 ± 1% and 21 ± 0.5 µg/mg, respectively, for cresol, with a full release of both drugs achieved after 180 min. The combination of both compounds exhibited a safe concentration of ≤6 µg/mL, with cell viability of >50% in human dermal fibroblasts (HFF-1) after 24 h. The MIC results indicated that the combination was efficient as an antibacterial agent against Gram-positive bacteria at a safe concentration. The shikonin/cresol-loaded fibrous system showed an inhibition zone close to that of the control drugs, suggesting that the drugs have retained their antibacterial activity after electrospinning. Conclusions: This dual drug-loaded fiber system showed a high potential as an antibacterial wound dressing for skin infection injuries. However, in vivo studies are required to assess the safety and efficacy in an animal model of the dual drug-loaded fiber system.

Pulmonary drug delivery has become a vital route for both local and systemic treatments because of the unique structure and function of the respiratory system. Unlike oral and injectable dosage forms, inhalation offers a non-invasive, direct route to deliver medicines to the lungs, bypassing gastric degradation and first-pass hepatic metabolism. Common forms such as aerosols, solutions, suspensions, and dry powders are frequently used to treat respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). However, their effectiveness is often limited by physiological and biopharmaceutical barriers, such as mucociliary clearance, enzymatic degradation, and nonspecific deposition, which reduce drug retention and bioavailability. These issues are especially critical for poorly soluble or sensitive molecules, leading to lower drug concentrations at the target site and necessitating frequent dosing. To address these challenges, advanced nanoparticle-based delivery systems are being developed to improve drug stability, targeting, and controlled release within the lungs. At the same time, computational methods, including deposition modeling, physiologically based pharmacokinetic (PBPK) simulations, and AI-driven optimization, are increasingly used in formulation development to predict in vivo performance and boost translational success. This review covers the physiological and biological barriers to pulmonary drug delivery, explores major inhalation routes and dosage forms, and discusses new therapeutic strategies and nanoparticle platforms. It also highlights the growing role of in silico modeling and AI in accelerating the design and optimization of pulmonary treatments, while addressing current challenges, limitations, and regulatory issues in translating pulmonary nanomedicine into clinical practice.

Antibiotic resistance poses a growing threat to public health, yet limited innovation and development of new antibacterial agents continue to hinder antibiotic discovery. Although only a few novel antibiotic candidates have passed clinical trials and reached the market, resistance continues to grow faster than antibiotic development. Despite numerous advances in drug development, using these technologies in isolation has constrained antibiotic discovery. This review examines how advanced technologies integrate into antibiotic drug discovery. It highlights a coupled approach (co-applied technologies) as an innovative strategy to mitigate the limitations of single approaches and accelerate lead discovery. By highlighting each technology and reviewing its potential applications, this strategy opens new routes and methods that can yield novel chemical scaffolds and new mechanisms of action (i.e., weakening microbial resistance), addressing the challenges posed by increasing global resistance and shortcomings in current antibiotic development. The review also addresses the challenges and barriers to discovering next-generation antibiotics. It also encourages researchers to implement platforms that combine coupled approaches and technologies, such as computational, genomic, biochemical, and structural tools, to replenish the next-generation antibiotic discovery pipeline and address the antimicrobial resistance (AMR) crisis. To strengthen global efforts and lessen the AMR crisis, an innovative antibiotic discovery strategy is necessary.