TR Dizin İndeksli Yayınlar Koleksiyonu / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/4
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Article Exploring Pi3k Pathway Inhibitors for Acute Myeloid Leukemia: a Drug-Repurposing Approach(Istanbul University Press, 2023-12-28) Ergun, Cansu; Kiremitci, Buse Zeren; Arslantas, Gizem; Bozkurt, Busenur; Duran, Gizem Ayna; Kiraz, YağmurObjective: Acute myeloid leukemia (AML) is a malignant disease characterized by the uncontrolled growth, differentiation, and proliferation of immature hematopoietic cells. Patients with AML often have poor survival rates, which are associated with specific gene mutations in FLT3, CEBPA, and NPM1. The phosphatidylinositol 3-kinase (PI3K) pathway, a lipase pathway, is activated in many malignancies, including AML. Given the low survival rates in AML, this study identified candidate drugs that could inhibit the PI3K pathway, thereby offering a potential treatment for AML, by using a drug-repurposing approach. Materials and Methods: Online bioinformatics tools were utilized to identify pathway-related genes and FDA-approved drugs. Subsequently, molecular docking was performed to determine the binding affinity values. Important genes were identified by evaluating their impact on survival and their aberrant expression in the tumor. In this study, genes such as VAV1, GSK3B, MTOR, PDPK1, PRR5, TSC2, AKT3, and CREB1 were determined and docked with their potential inhibitors. Particular attention was paid to VAV1 because there were no known potential VAV1 inhibitors used in AML. Results: The docking results were ranked, and the proposed gene–drug pairs were identified as tideglusib and fostamatinib for the inhibition of GSK3B, pimecrolimus and fostamatinib for the inhibition of MTOR, and fostamatinib for the inhibition of PDPK1. Furthermore, nebivolol, darifenacin, dihydroergotamine, libanserin and entereg were identified as potential inhibitors of VAV1 in AML. Conclusion: To sum up, most effective gene–drug pairs according to binding affinities were proposed as candidate inhibitor drugs for AML.Article Promoting Utilization of Biofuels in the Transportation Sector To Reduce Co2 Emissions: Comparative Analysis(Gazi Univ, 2022-12-16) Bozbay, Utku; Güngörmüşler, MineIn this study, due to the high contribution of the transportation sector to generate CO2 emissions, an evaluation for the best scenario of the replacement of petroleum derived fuels by renewable and sustainable alternatives was assessed with a multi collative approach suggesting the second-generation bioethanol as the most promising one. In this context, this paper focused on the practices over the past 23 years in the following four countries; Turkey, China, Sweden, and Brazil, with a comparative regression analysis between the CO2 emissions generated from the consumptions of total energy and biofuels. Accordingly, a curve-fitting and an estimation on the formation of CO2 emissions with the incrementing blends of gasoline by 3 to 100% of bioethanol was forecasted for 2020 to 2030. The outcomes of the comprehensive research indicated the international and national benefits of biofuel use, thus, promoting the potential integration of bioethanol in the Turkish transportation sector.Article In Silico Approach for Identification of PI3K/MTOR Dual Inhibitors for Multiple Myeloma Treatment(Istanbul Univ, 2023-04-14) Masalaci, Ilke; Akdogan, Yaren; Mutlu, Ozge; Eyvaz, Hande; Kiraz, YagmurObjective: Multiple myeloma is a hematologic malignancy in which targeting phosphoinositide 3 kinase (PI3K) and/or the mammalian target of rapamycin (mTOR) individually has been shown to have anti-proliferative effects, however, inhibiting both proteins simultaneously has been reported to have more effective results for its treatment. The aim of this study is to determine the molecular interactions and predicted inhibitory effects of 40 different dual inhibitors on mTOR, PI3K delta, and PI3K gamma to propose potentially the most effective dual inhibitor that targets the PI3K delta and PI3K gamma isoforms as well as the mTOR proteins since those isoforms are known to be predominant in multiple myeloma patients. Therefore, the focus in this study is built around the specific targeting of the PI3K delta and PI3K gamma isoforms from the multiple myeloma perspective. Materials and Methods: In silico docking experiments were conducted to determine the binding energies for different ligands that target mTOR, PI3K delta, and PI3K gamma. Protein-dual inhibitor complexes and the amino acids and bond types were visualized to identify molecular interactions. The absorption, distribution, metabolism, and excretion properties of dual inhibitors were analyzed and evaluated. Results: The binding affinity values were found to be between -7 and -9.9 kcal/mol. The toxicity prediction values of the selected dual inhibitors were obtained from the Pro-Tox-II web tool and classified according to the globally harmonized system of classification of labeling of chemicals. Conclusion: Correspondingly, among all dual inhibitors, Vistusertib is determined to be a promising compound against multiple myeloma cells by inhibiting both PI3K delta and PI3K gamma as well as mTORC1/2.