Background: The need to develop novel antimicrobial agents is apparent as infectious diseases are increasing and resistance is rapidly developing against the drugs used in the treatment. Objective: This study aimed at the synthesis, antimicrobial susceptibility testing, and computational elucidation of the mechanism of action of benzoxazole derivatives. It also aimed to compare the results obtained in this study with the previous studies by our group. This would pave the way for designing novel molecules with better antimicrobial activity. The other goal was pharmacophore analysis and in silico ADMET analysis of them. Methods: In this study, synthesis, antimicrobial susceptibility testing, molecular docking, pharmacophore analysis, and ADMET prediction were carried out. Results: The antimicrobial activity studies demonstrated that the synthesized compounds were active against standard strains and clinical isolates at high concentrations. Then, the antimicrobial testing results were compared to similar benzoxazoles tested by our group previously. Benzoxazole derivatives without a methylene bridge between oxazole and phenyl ring were found to be more active than those with the methylene bridge. This was also confirmed by molecular modeling undertaken in this study. The computational results indicated that the antibacterial activity could be achieved by DNA gyrase inhibition. Pharmacophore analysis showed that hydrogen bond acceptor (HBA), hydrogen bond donor (HBD), and hydrophobicity features would contribute to the inhibition. In addition, in silico ADMET property investigation of the compounds exhibited that they had the desired pharmacokinetics. Conclusion: Although antibacterial activity by inhibiting DNA gyrase is selective, the synthesized compounds were active at much higher concentrations than the standards. Therefore, in prospective antimicrobial studies, it is better to focus on benzoxazole derivatives without the methylene bridge. Since the compounds had suitable in silico ADMET properties, screening them against the other pharmacologic activities should be carried out. It is recommended to support the molecular modeling results with in vitro or in vivo studies.

In this study, the antimicrobial activities of previously synthesized 2-(substituted)oxazolo[4,5-b]pyridine derivatives toward six bacteria strains and twelve related drug-resistant isolates, and one fungus strain and two related drug-resistant isolates were investigated via the microdilution method. P6 (2-(4-trifluoromethylphenyl)oxazolo[4,5-b]pyridine) and P7 (2-(4-trifluoromethoxyphenyl)oxazolo[4,5-b]pyridine) showed better activity against E. faecalis isolate and E. coli isolate than ampicillin with a MIC of 16 μg mL⁻¹. In addition, P5 (2-(4-methoxyphenyl)oxazolo[4,5-b]pyridine) and P6 showed gentamicin-equivalent activity against P. aeruginosa, with a MIC of 16 μg mL⁻¹, while P7 showed better activity than gentamicin, with a MIC of 8 μg mL⁻¹. The compounds generally showed good to strong antimicrobial activities. Molecular docking and molecular dynamics simulations of the compounds were performed using the DNA gyrase enzyme, and the interactions were evaluated. The compounds showed an overlap at the DNA gyrase ATP binding site with similar protein–ligand interactions. Average RMSD values of the apo form, and P5-4KTN, P6-4KTN and P7-4KTN holo forms were measured to be 0.149 nm, 0.152 nm, 0.165 nm, and 0.146 nm, respectively. The P7 ligand stabilized the protein via further increasing its stability. HOMO–LUMO orbital energies and other electronic parameters derived from these energies, MEP and NBO analysis, and geometric optimization were obtained using DFT/B3LYP theory and the 6-311G(d,p) basis set. The LUMO–HOMO ΔE values for the most active compounds, P5, P6 and P7, are 4.3508, 4.4471, and 4.4852 eV, respectively. The predicted ADME profiles of the compounds were calculated, and they were compliant with Lipinski and other restrictive rules.

Biofilms are often responsible for the difficulties in the treatment of infectious diseases due to their properties that facilitate escape from antibiotic effect and their antiphagocytic effects. At least 65% of all infectious diseases are associated with biofilm-forming bacteria. As Staphylococcus aureus and Staphylococcus epidermidis are among the most common agents of hospital infections and the infections are mostly biofilm-related, they pose an important problem. In infectious isolates, the minimum biofilm eradication concentration (MBEK) values of biofilm forms are much higher than the minimum inhibition concentration (MIC) values of planktonic forms. This situation requires the use of much higher doses of antibiotics in the treatment of infections and causes an increase in antibiotic resistance. The N-acetylcysteine (NAC) molecule is known to be effective against biofilm by disrupting mature biofilms and reducing the adhesion of bacteria to surfaces. In this study, it was aimed to demonstrate i) the biofilm-forming abilities ii) the change in ampicillin and vancomycin MIC values in the presence of NAC molecules, iii) the change in the MBEK values of these antibiotics in the presence of NAC molecule and iv) the change in the expression levels of genes thought to be related to biofilm formation in the presence of the NAC molecule among S.aureus (n= 38) and S.epidermidis (n= 12) isolates isolated from various clinical specimens in Trakya University Health Research and Application Center. In this study, microplate crystal violet method was used to demonstrate the biofilm formation in staphylococci. Broth microdilution and checkerboard method were used to demonstrate the change in the presence of NAC molecule of the MIC and MBEC values of ampicillin and vancomycin. The effect of NAC on the expression of intercellular binding proteins A and D (icaA, icaD) and Staphylococcus regulatory protein A (sarA) genes, which are the genes involved in biofilm formation in staphylococci, was determined by quantitative real-time Polymerase Chain Reaction (qRt-PCR) method. The Student-t test was used to compare the control and experimental groups (concentrations detected with synergy and additive effect); p< 0.05 was accepted as the limit value of significance. In this study, when the NAC molecule was used together with ampicillin and vancomycin, it was determined that this combination lowers the MIC values of staphylococcus isolates and staphylococcal biofilm MBEK values; and also the expression levels of icaA, icaD and sarA which were effective in biofilm formation in staphylococci have not changed and decreased. As a result, in this study, it has been determined that the NAC molecule can be a new alternative for combined drug therapy and is promising in terms of bringing a new approach to treatment. In addition, it is thought that it is possible to use the NAC molecule together with different microorganisms and antimicrobial agents, and the results obtained in this study are considered to be guiding for further studies on this subject.

Sustainable utilization of agricultural waste in advanced polymeric materials offers an effective pathway toward environmentally responsible functional systems. In this study, cross‐linked poly(vinyl alcohol) (PVA) composite films reinforced with nitric acid–treated hard carbon (HNO ₃ ‐HC) derived from rice husk were successfully fabricated and systematically investigated. Hard carbon was obtained via high‐temperature pyrolysis and subsequently functionalized using nitric acid to improve interfacial compatibility and bioactivity. Composite films containing 1.0, 1.5, and 2.5‐wt% HNO₃‐HC were prepared by solution casting followed by vapor‐phase glutaraldehyde cross‐linking. SEM and EDX analyses confirmed homogeneous dispersion of HNO ₃ ‐HC within the PVA matrix, whereas FT‐IR results indicated enhanced hydrogen bonding interactions. Incorporation of HNO ₃ ‐HC improved thermal stability, increasing the glass transition temperature from 74.9°C (neat PVA) to 84.3°C for the 2.5‐wt% composite. Water contact angle values decreased from 43.9° to 34.9°, indicating enhanced surface hydrophilicity. Mechanical testing revealed a transition from stiffness‐dominated to ductility‐dominated behavior with increasing filler content, with the highest work at break (1426 N·mm) observed for PVA‐HC‐2.5. Antioxidant activity increased with filler loading, reaching 13.7% (DPPH) and 27.1% (ABTS) inhibition at 60 min for the PVA‐HC‐2.5 sample. Antibacterial assays demonstrated bacterial reduction of up to 72% against Staphylococcus aureus and 65% against Pseudomonas aeruginosa , also observed for PVA‐HC‐2.5. In addition, the lowest water contact angle (34.9°) was recorded for the same formulation. These findings establish rice husk–derived HNO ₃ ‐HC as a promising multifunctional biofiller for PVA, enabling the fabrication of sustainable composite films with consistent and measurable enhancements in antioxidant and antibacterial performance relative to pristine PVA.

The integration of nanotechnology with green chemistry presents sustainable strategies for developing multifunctional cosmeceutical formulations. In this study, iron oxide nanoparticles (IONPs) were successfully synthesized using antioxidant-rich green tea extract via an eco-friendly method. The nanoparticles were incorporated into a novel Pickering emulsion comprising coconut oil and green tea extract, targeting UV protection and antimicrobial performance. The green-synthesized IONPs displayed strong UV absorption properties, achieving an SPF of 6.20 at 1.0 M concentration, outperforming standard TiO₂ nanoparticles (SPF 3.98). The optimized Pickering emulsion formulation showed stability and skin-friendly pH. Antimicrobial studies revealed significant inhibition of Cutibacterium acnes and Staphylococcus aureus, with over 97% microbial reduction observed within 2 h of exposure. This dual-functional system, combining UV protection and antimicrobial effects, demonstrates the potential of green nanomaterials for developing safe, effective, and sustainable skincare formulations. The study provides new insight into the application of iron-based green nanotechnology in surfactant-free emulsions, supporting further innovation in the field of natural photoprotective cosmeceuticals.

Bu çalışmada, yeni 2-(p-Florofenil)-5-(2-(4-asetilpiperazin-1-il)asetamido)benzoksazol bileşiği üç aşamada sentezlenmiş ve yapısı 1H-NMR ve 13C-NMR spektroskopisi ile aydınlatılmıştır. Antimikrobiyal aktivite çalışmaları, Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii NTCC 13304, Klebsiella pneumoniae ATCC 700603, Candida albicans ATCC 10231 ve bunların izolatları izolatları üzerinde gerçekleştirildi. Antimikrobiyal aktivite sonuçlarına göre, referans ilaçlar genel olarak daha iyi antimikrobiyal aktivite göstermesine rağmen sentezlenen bileşik, MİK: 32 µg mL-1 ile ampisilin ile karşılaştırıldığında E. faecalis izolatları ve E. coli izolatları üzerinde oldukça umut verici aktivite gösterdi. Moleküler doking çalışması DNA giraz subunit B yapısı üzerinde gerçekleştirildi. Teorik ADME (absorbsiyon, dağılım, metabolizma, eliminasyon) özellikleri hesaplandı. Ayrıca DFT/B3LYP yöntemi ve 6-311G (d,p) temel seti kullanılarak HOMO-LUMO enerjileri, moleküler elektrostatik potansiyel analizi ve optimize edilmiş geometrik yapısı belirlendi ve sonuçlar görüntülendi.