Eczacılık Fakültesi / Faculty of Pharmacy
Permanent URI for this collectionhttps://hdl.handle.net/11727/5700
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Item Azoles Display Promising Anticonvulsant Effects Through Possible Ppar-Α Activation(Başkent Üniversitesi Eczacılık Fakültesi, 2024-05-25) Sari, Suat; Yurtoglu, Sibel; Zengin, Merve; Marcinkowska, Monika; Siwek, Agata; Sarac, SelmaAzoles such as nafimidone, denzimol and loreclezole are known for their clinical efficacy against epilepsy, and loreclezole acts by potentiating gamma-aminobutyric acid (GABA)-ergic currents. In the current study, we report a series of azole derivatives in alcohol ester and oxime ester structure showing promising anticonvulsant effects in 6 Hz and maximal electro shock (MES) models with minimal toxicity. The most promising of the series, 5f, was active in both 6 Hz and MES tests with a median effective dose (ED50) of 118.92 mg/kg in 6 Hz test and a median toxic dose (TD50) twice as high in mice. The compounds were predicted druglike and blood-brain barrier (BBB) penetrant in silico. Contrary to what was expected, the compounds showed no in vitro affinity to GABAA receptors (GABAARs) in radioligand binding assays; however, they were found structurally similar to peroxisome proliferator-activated receptors alpha (PPAR-alpha) agonists and predicted to show high affinity and agonist-like binding to PPAR-alpha in molecular docking studies. As a result, 5f emerged as a safe azole anticonvulsant with a wide therapeutic window and possible action through PPAR-alpha activation.Item Comparative Plant Metabolomics of Momordica charantia Seeds and Fruits(Başkent Üniversitesi Eczacılık Fakültesi, 2024-03-30) Enes, Duygu; Fidan, Bilge Basak; Basaran, Arif Ahmet; Celebier, MustafaMomordica charantia L., Cucurbitaceae, known mainly as karela, bitter gourd or bitter melon, and balsam pear, is used for antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer, and anti-inflammatory and wound healing. This study aimed to elucidate the differences in the metabolites of 70% methanol extracts of M. charantia seeds and fruit using untargeted metabolomics. Liquid chromatography coupled to quadrupole time-of-flight mass spectrometry-based analysis of the extracts for both seed and fruit was performed using a C-18 column. Differences were observed in seed and fruit extracts, which were visualized using principal component analysis plots. (R)-Salsolinol, pantetheine, coumarin, tryptamine, lysophospholipidPC(O-18:0), glucosylceramide, pyroglutamic acid, and presqualene diphosphate in the seed and fruit of M. charantia were detected in different levels. The amount of lysophospholipidPC(O-18:0) (lysoPC(O-18:0)) and glucosylceramide is high in the fruit, while the amount of (R)-salsolinol, pantetheine, coumarin, tryptamine, presqualene diphosphate, and pyroglutamic acid is high in the seed. These primary untargeted metabolomic results revealed that the different pharmacological effects may be related to the variable amounts of some specific metabolites in seeds and fruits.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 Tanju
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