Moleküler Biyoloji ve Genetik Bölümü Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/209

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Browsing Moleküler Biyoloji ve Genetik Bölümü Koleksiyonu by Author "0000-0002-5444-3929"

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    Article
    Determination of promising inhibitors for N-SH2 domain of SHP2 tyrosine phosphatase: an in silico study
    (SPRINGER NATURE LINK, 2024) Akcok, Emel Basak Gencer; Guner, Huseyin; Akcok, Ismail; 0000-0002-6559-9144; 0000-0002-5444-3929; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü; Akcok, Emel Basak Gencer; Akcok, Ismail
    There 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.
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    Article
    Ethacrynic acid and cinnamic acid combination exhibits selective anticancer effects on K562 chronic myeloid leukemia cells
    (SPRINGER, 2022) Yenigul, Munevver; Akcok, Ismail; Gencer Akcok, Emel Basak; 0000-0002-6559-9144; 0000-0002-5444-3929; 0000-0003-0468-721X; AGÜ, Yaşam ve Doğa Bilimleri Fakültesi, Biyomühendislik Bölümü; Yenigul, Munevver; Akcok, Ismail; Gencer Akcok, Emel Basak
    Background Despite the recent advances in chemotherapy, the outcomes and the success of these treatments still remain insufficient. Novel combination treatments and treatment strategies need to be developed in order to achieve more effective treatment. This study was designed to investigate the combined effect of ethacrynic acid and cinnamic acid on cancer cell lines. Methods The anti-proliferative effect of ethacrynic acid and cinnamic acid was investigated by MTT cell viability assay in three different cancer cell lines. Combination indexes were calculated using CompuSyn software. Apoptosis was assessed by flow cytometric Annexin V-FITC/PI double-staining. The effect of the inhibitors on cell cycle distribution was measured by propidium iodide staining. Results The combination treatment of ethacrynic acid and cinnamic acid decreased cell proliferation significantly, by 63%, 75% and 70% for K562, HepG2 and TFK-1 cells, respectively. A 5.5-fold increase in the apoptotic cell population was observed after combination treatment of K562 cells. The population of apoptotic cells increased by 9.3 and 0.4% in HepG2 and TFK-1 cells, respectively. Furthermore, cell cycle analysis shows significant cell cycle arrest in S and G2/M phase for K562 cells and non-significant accumulation in G0/G1 phase for TFK-1 and HepG2 cells. Conclusions Although there is a need for further investigation, our results suggest that the inhibitors used in this study cause a decrease in cellular proliferation, induce apoptosis and cause cell cycle arrest.