Eczacılık Fakültesi / Faculty of Pharmacy
Permanent URI for this collectionhttps://hdl.handle.net/11727/5700
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Item Azole Rings Linked To Cox Inhibitors Via Hydrazone Bridge: Synthesis, Stereochemical Analysis, And Investigation Of Antimicrobial Activity(Başkent Üniversitesi Eczacılık Fakültesi, 2024-04-19) Karaguzel, Ayse; Ugur, Suemeyye Buran; Cetinkaya, Yasin; Dogan, Senguel Dilem; Stevanovic, Milena; Nikodinovic-Runic, Jasmina; Gunduz, Miyase GozdeNonsteroidal anti-inflammatory drugs (NSAIDs) alleviate inflammation and pain through the inhibition of cyclooxygenase (COX) enzymes. Besides these widely recognized therapeutic utilizations, NSAIDs have been reported to display moderate antimicrobial activity and enhance antimicrobial efficacy when administered in combination with commercial antimicrobial drugs. In the present study, we designed novel potential antimicrobial agents by linking some NSAIDs (ibuprofen, flurbiprofen, and naproxen) to various azole rings (pyrazole, imidazole, triazole, and benzimidazole) via hydrazone functionality. The hydrazone linker was introduced into the chemical scaffold of the title molecules by the reaction between hydrazides obtained from NSAIDs and inhouse synthesized azole-carrying benzaldehydes. The structures of the target compounds were elucidated by a combination of spectral methods. The NOESY spectra and stereochemical analyses performed using DFT method confirmed the presence of the target molecules as a mixture of E(C=N)-E(N-N)-synperiplanar and E(C=N)-E(N-N)antiperiplanar conformers in DMSO-d6 solution. 1H and 13C NMR chemical shift values in DMSO were calculated using the GIAO method and compared with the experimental NMR data. Finally, some derivatives were demonstrated to inhibit Candida albicans filamentation and/or bacterial communication system known as quorum sensing. For COX inhibitor-azole hybrids with antimicrobial potency, naproxen appeared to be the most appropriate NSAID, while bulky benzimidazole was not found as a preferable azole ring.Item The Clinical Efficacy of Adding Ceftazidime/Avibactam to Standard Therapy in Treating Infections Caused by Carbapenem-Resistant Klebsiella pneumonia with blaOXA-48-like Genes(Başkent Üniversitesi Eczacılık Fakültesi, 2024-04-03) Jaber, Al Maamon R. Abu; Basgut, Bilgen; Hawan, Ali Abdullah; Al Shehri, Ali Amer; AlKahtani, Sultan Ahmad; Ahmed, Nehad J.; Abdi, AbdikarimCeftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant Enterobacterales pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the Armed Forces Hospital in the southern region of Saudi Arabia to compare the clinical and microbiological outcomes for CAZ-AVI-treated patients as monotherapy and as an add-on to standard therapy for carbapenem-resistant Klebsiella pneumonia (CRKP) OXA-48 infections to those treated with standard drugs. The study included CRKP OXA-48-like infected patients who were administered antibiotics for more than seven days from 1 August 2018 to May 2023. Patients' baseline characteristics and demography were extracted from the clinical records, and their clinical/microbiology efficiencies were assessed as per the corresponding definitions. Univariate and multivariate logistic regressions were conducted to identify the potential independent variable for CAZ-AVI efficiency. A total of 114 patient files were included for the evaluation. Among these patients, 64 used CAZ-AVI combined with standard therapy and were included in the intervention group, and 50 of them used standard therapy and were included in the comparative group. Following analysis, CAZ-AVI's clinical success was 42.2% (p = 0.028), while the intervention versus comparative groups showed decreased 30-day all-cause mortality (50.0% versus 70.0%; p = 0.036) and infection recurrence (7.8% versus 24.0%; p = 0.019), as well as substantially increased rates of microbial eradication (68.8% versus 42.0%; p = 0.007). CAZ-AVI add-on therapy rather than monotherapy showed statistically significant favored clinical and microbial outcomes over the standard therapy. Furthermore, sex (female %), ICU admission, and fever were negatively associated with patients' 30-day all-cause mortality, serving as independent negative factors. Only fever, CRP bio levels, inotropes, and ICU admissions were significant predictors influencing the CAZ-AVI's clinical efficiency. The duration of CAZ-AVI therapy positively influenced CAZ-AVI's microbial eradication, while both WBC counts and fever experiences were negative predictors. This study shows the effective usage of CAZ-AVI against CRKP OXA-48-like infections. The influencing independent variables depicted here should recommend that clinicians individualize the CAZ-AVI dose based on co-existing risk factors to achieve optimal survival and efficacy. Prospective multicenter and randomized control studies are recommended, with individualized CAZ-AVI precision administration implemented based on patients' characteristics.Item Antimicrobial Dosing Recommendations During Continuous Renal Replacement Therapy: Different Databases, Different Doses(Başkent Üniversitesi Eczacılık Fakültesi, 2024-03-27) Pehlivanli, Aysel; Yalcin, Tugba Yanik; Yesiler, Fatma Irem; Sahinturk, Helin; Azap, Ozlem Kurt; Zeyneloglu, Pinar; Basgut, BilgenMeticulous antimicrobial management is essential among critically ill patients with acute kidney injury, particularly if renal replacement therapy is needed. Many factors affect drug removal in patients undergoing continuous renal replacement therapy CRRT. In this study, we aimed to compare current databases that are frequently used to adjust CRRT dosages of antimicrobial drugs with the gold standard. The dosage recommendations from various databases for antimicrobial drugs eliminated by CRRT were investigated. The book 'Renal Pharmacotherapy: Dosage Adjustment of Medications Eliminated by the Kidneys' was chosen as the gold standard. There were variations in the databases. Micromedex, UpToDate, and Sanford had similar rates to the gold standard of 45%, 35%, and 30%, respectively. The Micromedex database shows the most similar results to the gold standard source. In addition, a consensus was reached as a result of the expert panel meetings established to discuss the different antimicrobial dose recommendations of the databases.Item Chymotrypsin and Trypsin Inhibitory Activity of Some Medicinal Plants Collected from Rize (Türkiye)(Başkent Üniversitesi Eczacılık Fakültesi, 2024-02-25) Gunbatan, Tugba; Sucu, Melike; Gokbulut, Alper; Dilmac, Elif; Gurbuz, IlhanIn this research, the evaluation of in vitro chymotrypsin and trypsin inhibitory activities of ten plant species collected from Rize were aimed, and fractions that showed strong activity were analyzed through HPLC. Daphne pontica L. and Mentha longifolia (L.) L. were found to have the highest chymotrypsin inhibitory activities (87.75 and 84.24 % inhibition). Similarly, the highest trypsin inhibitory activity was observed in D. pontica (%99.93 inhibition), followed by Sambucus ebulus L. flowers (87.47 % inhibition). Extracts showing strong enzyme inhibition were fractioned and subjected to activity tests. The highest chymotrypsin inhibitory activity was observed in the n-hexane fraction of D. pontica (%80.70 inhibition), while the highest trypsin inhibitory activity was found in the n-butanol fraction of S. ebulus (%86.81 inhibition). HPLC studies determined that the 80 % ethanol extract of D. pontica and its dichloromethane and ethyl acetate fractions contained umbelliferone. It was found that chlorogenic acid was present in the 80 % ethanol extracts of S. ebulus flowers. M. longifolia was found to contain chlorogenic acid, caffeic acid, luteolin-7-glucoside, and rosmarinic acid. M. longifolia has been identified as the plant exhibiting the highest antioxidant activity in ABTS and CUPRAC tests, consistent with its high phenolic and flavonoid content.Item Antimicrobial De-Escalation in Intensive Care Unit: Theory and The Reality?(Başkent Üniversitesi Eczacılık Fakültesi, 2024-02-01) Pehlivanli, Aysel; Ozgun, Cigdem; Solmaz, Firdevs Gonca Sasal; Yuksel, Didem; Basgut, Bilgen; Ozcelikay, Arif Tanju; Unal, Mustafa NecmettinItem Antimicrobial Use In Palliative Care Service: A Prevalence Study(Başkent Üniversitesi Eczacılık Fakültesi, 2024-02-01) Bicer, Asim Emre; Pehlivanli, Aysel; Basgut, Bilgen; Ozcelikay, Arif TanjuItem An Essential Problem in Antimicrobial Stewardship: Multi-Drug-Resistant Gram-Negative Bacterial Infection in the Intensive Care Unit(Başkent Üniversitesi, 2024-02-01) Pehlivanli, Aysel; Ozgun, Cigdem; Yuksel, Didem; Solmaz, Firdevs Gonca Sasal; Ozcelikay, Arif Tanju; Unal, Mustafa NecmettinItem The Impact of Clinical Pharmacist in Geriatric Drug-Related Problems: A Scoping Review(Başkent Üniversitesi, 2024-02-01) Ediz, Cigdem; Bicer, Asim Emre; Pehlivanli, Aysel; Basgut, Bilgen; Ozcelikay, Arif TanjuItem Electrospun Hesperidin Nanofibers Induce A Cytoprotective Effect On Sodium-Fluoride Induced Oxidative Stress In Vitro(JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 2024-03-08) Birer, Mehmet; Kara, Adnan Altug; Yurdakok-Dikmen, Begum; Uyar, Recep; Aralan, Gizem; Birer, Yagmur Turgut; Filazi, Ayhan; Acartuerk, FusunAs a bioactive flavonoid in Citrus seeds, hesperidin exerts significant antioxidant, free radical scavenging, and anticancer activity with limited bioavailability. To enhance the stability and improve the bioactive potential of hesperidin, an electrospun nanofiber formulation was developed. Electrospinning solution was characterized by surface tension, viscosity, and conductivity measurements, and these values were found to be 25.18 +/- 0.04 mN/ m 145 +/- 2 cPs and 9.0 +/- 0.4 mu S/cm, respectively. Electrospun hesperidin nanofiber was tested in a coincubation with the cytotoxic agent sodium fluoride (NaF) in Caco-2 cells. Inhibitory concentration-50 (IC50) values of hesperidin nanofiber in Caco-2 cells alone were as low as 30 mu M, indicating its potential anticancer effect, while coincubation with 10 and 20 mu M of hesperidin nanofibers was found to alleviate the cytotoxic effect induced by NaF at 2.1, 1.05 and 0.525 mM concentrations. This effect was in accordance with cellular antioxidant mechanisms; where malondialdehyde (MDA) levels at 10 mu M hesperidin nanofiber were found to be decreased by 55.60% in the thiobarbituric acid reactive substances (TBARS) assay, and the mRNA expression of Thioredoxin1 (TRX1) and Superoxide dismutase-1 (SOD1) were decreased in qPCR. The results revealed that electrospun nanofiber of hesperidin was developed for the first time with useful implications against cellular toxicity by alleviating the cellular antioxidant defense mechanisms, including MDA, SOD1, and TRX1.Item Cerliponase Alfa Decreases Aβ Load And Alters Autophagy- Related Pathways In Mouse Hippocampal Neurons Exposed To Faβ1-42(LIFE SCIENCES, 2024-11-15) Kose, Selma; Cinar, Elif; Akyel, Hilal; Cakir-Aktas, Canan; Tel, Banu Cahide; Karatas, Hulya; Kelicen-Ugur, PelinExtracellular aggregation of amyloid-beta (A beta) in the brain plays a central role in the onset and progression of Alzheimer's disease (AD). Moreover, intraneuronal accumulation of A beta via oligomer internalization might play an important role in the progression of AD. Deficient autophagy, which is a lysosomal degradation process, occurs during the early stages of AD. Tripeptidyl peptidase-1 (TPP1) functions as a lysosomal enzyme, and TPP1 gene mutations are associated with type 2 late infantile neuronal ceroid lipofuscinosis (LINCL). Nevertheless, there is little information about the role of TPP1 in the pathogenesis of AD; therefore, the present study aimed to measure the decrease in intraneuronal A beta accumulation by a recombinant analog of the TPP1 enzyme, cerliponase alfa (CER) (Brineura (R)), and to determine whether autophagy pathways play a role in this decrease. In this study, endogenous A beta accumulation was induced by fA beta(1-42) (a toxic fragment of full-length A beta) exposure, and mouse hippocampal neuronal cells (HT-22) were treated with CER (human recombinant rhTPP1 1 mg mL-1). Soluble A beta, TPP1, and the proteins involved in autophagy, including mammalian target of rapamycin (p-mTOR/ mTOR), p62/sequestosome-1 (p62/SQSTM1), and microtubule-associated protein 1 A/1B-light chain 3 (LC3), were evaluated using western blotting. The sirtuin-1, beclin-1, and Atg5 genes were also studied using RT-PCR. A beta and TPP1 localizations were observed via immunocytochemistry. CER reduced the A beta load in HT-22 cells by inducing TPP1 expression and converting pro-TPP1 into the mature form. Furthermore, exposure to CER and fA beta(1-42) induced the autophagy-regulatory/related pathways in HT-22 cells and exposure to CER alone increased sirtuin-1 activity. Based on the present findings, we suggest that augmentation of TPP1 with enzyme replacement therapy may be a potential therapeutic option for the treatment of AD.