WoS İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6
Browse
3 results
Search Results
Article Metabolic Responses to Benzoic Acid Stress and Glutamine Transport-Dependent Vulnerabilities in Escherichia Coli Revealed by NMR Metabolomics(Springer, 2026) Yuksektepe, Ecem; Elgin, Emine Sonay; Onat-Tasdelen, Kadriye Aslihan; Chae, Young Kee; Dogu, Eralp; Catav, Sukru Serter; Ozturkel-Kabakas, HaticeBenzoic acid (BA) is a widely used weak organic acid preservative with antimicrobial activity, yet the metabolic basis of its antibacterial action and the determinants of bacterial sensitivity remain incompletely understood. Here we combined growth assays with H-1 NMR metabolomics to characterize BA-induced metabolic responses in Escherichia coli BW25113 and to examine metabolic changes associated with impaired glutamine transport. Wild-type BW25113 and its BA-sensitive isogenic Delta glnP mutant, lacking the membrane-bound glutamine permease of the high-affinity GlnHPQ transport system, were exposed to sublethal BA concentrations. BA slowed growth and significantly altered the levels of 42 metabolites in the wild-type and 38 in Delta glnP, with the mutant showing stronger growth inhibition and reduced BA tolerance. Both strains exhibited metabolic changes consistent with cellular responses to oxidative and acid stress, including alterations in central carbon metabolism, lysine degradation, cysteine and methionine metabolism, pyrimidine metabolism, and one-carbon pool by folate. However, several metabolic responses differed between the two strains. In wild-type cells, BA exposure was associated with changes in glycerolipid metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, lysine biosynthesis, glycine, serine and threonine metabolism, and purine metabolism. In contrast, Delta glnP cells showed distinct alterations in D-amino acid metabolism, arginine biosynthesis, and other carbon fixation pathways. In addition, the mutant displayed substantial baseline differences relative to the wild-type, including altered nucleotide and amino acid pools. Together, these results indicate that both BA exposure and deletion of glnP induce broad metabolic adjustments in Escherichia coli. Loss of glnP is associated with distinct metabolic states and altered responses to BA stress, highlighting the importance of glutamine transport in adaptation to weak organic acid stress.Article Citation - WoS: 2Citation - Scopus: 2Synthesis of Novel Thiazole/Thiadiazole Conjugates of Fluoroquinolones as Potent Antibacterial and Antimycobacterial Agents(John Wiley and Sons Inc, 2025) Poyraz Yılmaz, P.; Kulabaş, N.; Bozdeveci, A.; Vagolu, S.K.; Imran, M.; Tatar, E.; Küçükgüzel, İ.; Yilmaz, Pinar PoyrazTwenty azole-fluoroquinolone hybrids were designed and synthesized by conjugating thiazole and thiadiazole structures to ciprofloxacin and norfloxacin via a 2-oxoethyl bridge. The structures and purities of the synthesized compounds were proven by spectral techniques. The antimycobacterial effects of target compounds 21–40 were tested against Mycobacterium tuberculosis H37Rv strain. Among the 20 synthesized compounds, 12 exhibited minimal inhibition concentration (MIC) values in the range of 1.56–25 μg/mL. Among the molecules screened for antimycobacterial effects, the most effective was compound 35, a thiadiazole-ciprofloxacin hybrid. The cytotoxic effect of this molecule was found to be lower than the reference drugs, and it was also determined to be a more effective inhibitor than ciprofloxacin and norfloxacin in the DNA-gyrase supercoiling test. The antimicrobial effects of compounds 21–40 were screened by agar-well diffusion and microdilution tests against Gram-positive/negative bacteria, a fast-growing mycobacterium, and two yeast strains. While most of the compounds tested showed antibacterial effects, the most effective fluoroquinolone derivative appeared to be compound 31 with an MIC value of < 0.63 μg/mL against all Gram-negative bacteria tested. Azole-fluoroquinolone hybrids 21–40 did not show any activity against non-pathogenic Lactobacillus species and yeast-like fungi, indicating that they have selective antibacterial and antimycobacterial activity, particularly against Gram-negative bacteria. In silico molecular docking studies were conducted to uncover the interactions between lead compound 35 and the DNA gyrase proteins of M. tuberculosis and S. aureus. Additionally, a 100 ns molecular dynamics simulation was carried out to assess the stability of the complexes formed between compound 35 and both proteins. © 2025 The Author(s). Chemical Biology & Drug Design published by John Wiley & Sons Ltd.Article Citation - WoS: 11Citation - Scopus: 11Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of New Thiosemicarbazide-Triazole Hybrid Derivatives of (<i>s</I>)-naproxen(Wiley-v C H verlag Gmbh, 2022) Han, M. Ihsan; Ince, Ufuk; Gunduz, Miyase Gozde; Kucckguzel, S. Guniz; Küçükgüzel, Ş. GünizThe discovery of new antimicrobial molecules is crucial for combating drug-resistant bacterial and fungal infections that pose a dangerous threat to human health. In the current research, we applied a molecular hybridization approach to synthesize original thiosemicarbazide-triazole derivatives starting from (S)-naproxen (7a-7k). After structural characterization using FT-IR, H-1-NMR, C-13-NMR, and HR-MS, the obtained compounds were screened for their antimicrobial activities against Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Candida albicans ATCC 10231 and their isolates, as well. Although all compounds were found to be moderate antimicrobial agents, in general, their antibacterial activities were better than antifungal effects. Among the tested compounds, 7j carrying nitrophenyl group on the thiosemicarbazide functionality represented the best MIC value against S. aureus isolate. Finally, molecular docking studies were performed in the active pocket of S. aureus flavohemoglobin to rationalize the obtained biological data.