Scopus İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/395
Browse
3 results
Search Results
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.Article Discovery of New Candidates Targeting the SH2 Domains of Spleen Tyrosine Kinase (Syk) Through in Silico Studies(Wiley-VCH Verlag GmbH, 2025-06) Sansacar, Merve; Sari, Ceyhun; Yucel, Muhsin Samet; Akcok, Emel Basak Gencer; Akcok, Ismail; Gencer Akçok, Emel BaşakSrc homology 2 (SH2) domains have become an increasingly popular candidate for researchers to search for novel therapeutics to target different diseases. Spleen tyrosine kinase (Syk) is one of the proteins with two SH2 domains that has a role in the pathogenesis of many diseases. Here, we report the discovery of a promising natural product (NP) inhibitor that targets the N-terminal SH2 (N-SH2) and C-terminal SH2 (C-SH2) domains of Syk simultaneously, through structure-based drug discovery approach. Molecular docking studies, followed by molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations, were utilized to reveal the interactions between NPs from "the COlleCtion of Open NatUral producTs (COCONUT)" database and Syk enzyme. Five natural products that have lowest Scoring and Minimization with AutoDock Vina (SMINA) scores against both SH2 domains of Syk were selected for further studies and compound CNP0265345 has the best binding free energies toward both C-SH2 and N-SH2 of Syk enzyme with -44.54 and -55.98 kcal/mol, respectively. Drug-likeness properties, absorption, distribution, metabolism, and excretion (ADME) and carcinogenicity predictions were also studied. In conclusion, our work highlights a novel drug candidate to target the Syk enzyme of SH2 domains using in silico methods.Article Citation - WoS: 3Citation - Scopus: 3Determination of Promising Inhibitors for N-SH2 Domain of SHP2 Tyrosine Phosphatase: An in Silico Study(Springer, 2024-05-13) Akcok, Emel Basak Gencer; Guner, Huseyin; Akcok, Ismail; Gencer Akçok, Emel BaşakThere are many genes that produce proteins related to diseases and these proteins can be targeted with drugs as a potential therapeutic approach. Recent advancement in drug discovery techniques have created new opportunities for treating variety of diseases by targeting disease-related proteins. Structure-based drug discovery is a faster and more cost-effective approach than traditional methods. SHP2 phosphatase, encoded by the PTPN11 gene, has been the focus of much attention due to its involvement in many types of diseases. The biological function of SHP2 is enabled mostly by protein-protein interaction through its SH2 domains. In this study, we report the identification of a potential small molecule inhibitor for the N-SH2 domain of SHP2 by structure-based drug discovery approach. We utilized molecular docking studies, followed by molecular dynamics simulations and MM/PBSA calculations, to analyze compounds retrieved from the Broad's Drug Repurposing Hub and ZINC15 databases. We selected 10 hit compounds with the best docking scores from the libraries and examined their binding properties in the N-SH2 domain. We found that compound CID 60838 (Irinotecan) was the most suitable compound with a binding free energy value of - 64.45 kcal/mol and significant interactions with the target residues in the domain.