Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
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Article Identification of Potential Dual HDAC6 and HSP90 Inhibitors for the Treatment of Cancer Using Molecular Docking, Molecular Dynamics and MM/PBSA Studies: A Comprehensive In Silico Study(Bentham Science Publ Ltd, 2026) Yucel, Muhsin Samet; Akcok, IsmailBackground Histone deacetylase 6 (HDAC6) and heat shock protein 90 (Hsp90) are crucial therapeutic targets in cancer research with their interconnected roles in regulating protein homeostasis and cellular processes. The interaction of these proteins within the cytosolic complex plays a critical role in regulating cancer cell survival and progression. Notably, current studies highlight that the simultaneous inhibition of HDAC6 and Hsp90 can produce synergistic effects and offer a promising therapeutic potential for combating malignant cancers.Objective The objective of this study was to explore potential compounds that can inhibit both HDAC6 and Hsp90 proteins.Methods In this study, a number of in-silico computational techniques were employed. A total of 791 molecules, sharing at least 30% similarity with previously identified four HDAC inhibitors, were obtained from the ZINC15 database and subjected to docking on HDAC6 and Hsp90 proteins. The top eight ligands demonstrating the best binding scores against both targets, with panobinostat and ganetespib serving as reference compounds for HDAC6 and Hsp90, respectively, were selected for further analysis. Subsequently, ADME prediction and molecular dynamics simulations were conducted on the selected ligands.Results A detailed molecular docking, molecular dynamics simulations and ADME studies have revealed that ZINC27653366 exhibited the highest inhibitory potential against both Hsp90 and HDAC6 target proteins, making it the most promising inhibitor.Conclusion In conclusion, although additional in vitro and in vivo studies are required for the validation, in silico evaluation of ZINC27653366 may position it as a promising candidate for the treatment of different types of cancers.Conference Object Citation - Scopus: 3A Computational Drug Repositioning Effort Using Patients' Reviews Dataset(Institute of Electrical and Electronics Engineers Inc., 2023-07-25) Akkaya, Ali; Bakal, GokhanThe drug discovery process is one of the core motivations in both medical and, specifically, pharmaceutical disciplines. Due to the nature of the process, it requires an excessive amount of time, clinical experiments, and budget to cover each discovery phase. In this sense, computational drug discovery efforts can shorten the discovery process by providing plausible candidates since many of the attempts fail for several reasons, such as a lack of participants, financial problems, or ineffective results. In this study, the goal is to identify plausible candidate drugs for diseases. To do that, we utilize a personal experience of drugs dataset generated by patients. Beyond the user-generated comments, the users also give a rate between 1 and 10. Since we want to ensure the dataset quality, we first performed sentiment analysis experiments to prove that the reviews/comments are consistent with the given rating score. Then, only the review pairs having an effectiveness rate of 6 or more are selected as pre-filtered drug-disease pairs. We also build a knowledge graph using treatment-related biomedical relations using predications from Semantic Medline Database to identify drug similarities utilizing the Simrank similarity algorithm. As a result, we reported a list of plausible drugs as repurposing/repositioning candidates for further experiments. © 2023 Elsevier B.V., All rights reserved.