Browsing by Author "Ozdemir, Zeynep"

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Does Theobromine Increase the Apoptotic Effect of STI571?
(2016) Kasap, Yesim Korkmaz; Ozdemir, Zeynep; Asparuk, Cagan; Ak, Oguzhan; Aysun, Dide; Akgor, Doga; Elmastas, Fulya; Akkus, Dogukan; Yurtcu, Erkan; 0000-0003-4930-8164; AAA-2998-2021
Objective: STI571, a selective tyrosine kinase inhibitor is used in CML chemotherapy. It has limited effects in some cases due to drug resistance and intoxication as other chemotherapeutic agents. Thus, many cancer patients use dietary supplements and herbal extracts for increasing the effectiveness of chemotherapeutic agents. Theobromine, a metabolite of cacao has prooxidant effects and regulates intercellular signaling pathways. The aim of the study is to determine the potential apoptotic effects of STI571 and theobromine on K562 cells, when used alone and in combination. Methods: Inhibitory concentrations of STI571 and theobromine were determined by MTT method. Both agents were applied to the cells at 48 h time period alone and in combination. Caspase activities were assessed colorimetrically. Apoptosis and necrosis were evaluated by using acridine orange/ethidium bromide staining. p<0.05 was considered as statistically significant. Results: Caspase activities increased when both agents administrated alone. Theobromine increased effects of STI571 on caspase activities in time and type dependent manner (p<0.05). Apoptotic cell rates also increased when two agents applied in combination (p<0.05) in time dependent manner. Theobromine also reduced necrotic cell rates. Conclusion: Although there are limited data about the intracellular effects of theobromine, we showed that theobromine has effects on the caspase pathway related apoptotic response carried out by STI571. We believe that this in vitro study will shed light for further researches.
Potent Antimicrobial Azoles: Synthesis, In Vitro and In Silico Study
(ANTIBIOTICS-BASEL, 2024-11) Ozdemir, Zeynep; Zenni, Yaren Nur; Karakurt, Arzu; Sari, Suat; Sarac, Selma; Akdag, Mevluet; Merde, Irem Bozbey; Kart, Didem; Venanzoni, Roberto; Flores, Giancarlo Angeles; Angelini, Paola; Kabier, Muzammil; Mathew, Bijo; Carradori, Simone
Background/Objectives: The increase in fungal infections, both systemic and invasive, is a major source of morbidity and mortality, particularly among immunocompromised people such as cancer patients and organ transplant recipients. Because of their strong therapeutic activity and excellent safety profiles, azole antifungals are currently the most extensively used systemic antifungal drugs. Antibacterial properties of various topical antifungals, such as oxiconazole, which features oxime ether functionality, were discovered, indicating an exciting prospect in antimicrobial chemotherapy. Methods: In this study, eleven new oxime ether derivatives with the azole scaffold (5a-k) were synthesized and tested for their antimicrobial effects using the microdilution method to obtain broad-spectrum hits. Results: Although the title compounds showed limited efficacy against Candida species, they proved highly effective against dermatophytes. Compounds 5c and 5h were the most potent derivatives against Trichophyton mentagrophytes and Arthroderma quadrifidum, with minimum inhibitory concentration (MIC) values lower than those of the reference drug, griseofulvin. The MIC of 5c and 5h were 0.491 mu g/mL and 0.619 mu g/mL against T. mentagrophytes (MIC of griseofulvin: 2.52 mu g/mL). The compounds were also tested against Gram-positive and Gram-negative bacteria. Briefly, 5c was the most active against Escherichia coli and Bacillus subtilis, with MIC values much better than that of ciprofloxacin (MIC of 5c = 1.56 mu g/mL and 1.23 mu g/mL, MIC of ciprofloxacin = 31.49 and 125.99 mu g/mL, respectively). Molecular docking suggested a good fit in the active site of fungal lanosterol 14 alpha-demethylase (CYP51) and bacterial FtsZ (Filamenting temperature-sensitive mutant Z) protein. Conclusions: As a result, the title compounds emerged as promising entities with broad antifungal and antibacterial effects, highlighting the utility of oxime ether function in the azole scaffold.