WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7150

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Institution Author: search.filters.institutionAuthor.Çetinkaya, Hakkı

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  • Article
    Citation - WoS: 2
    Citation - Scopus: 2
    Novel 2 '-alkoxymethyl Substituted Klavuzon Derivatives as Inhibitors of Topo I and Crm1
    (Academic Press, 2020) Çetinkaya, Hakkı; Çağır, Ali; Yıldız, Mehmet Salih; Kutluer, Meltem; Alkan, Aylin; Otaş, Hasan Ozan; Çağır, Ali; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    In this work, 2'-alkoxymethyl substituted klavuzon derivatives were prepared starting from 2-methyl-1-naphthoic acid in eight steps. Anticancer potencies of the synthesized compounds were evaluated by performing MTT cell viability test over cancerous and healthy pancreatic cell lines, along with CRM1 inhibitory properties in HeLa cells by immunostaining and Topo I inhibition properties by supercoiled DNA relaxation assay. Their cytotoxic activities were also presented in hepatocellular carcinoma cells (HuH-7) derived 3D spheroids. Among the tested klavuzon derivatives, isobutoxymethyl substituted klavuzon showed the highest selectivity of cytotoxic activity against pancreatic cancer cell line. They showed potent Topo I inhibition while their CRM1 inhibitory properties somehow diminished compared to 4'-alkylsubstituted klavuzons. The most cytotoxic 2'-methoxymethyl derivative inhibited the growth of the spheroids derived from HuH-7 cell lines and PI staining exhibited time and concentration dependent cell death in 3D spheroids.
  • Conference Object
    A Novel Inhibitor for Krasg12c Mutant Lung Carcinoma
    (International Association for the Study of Lung Cancer, 2020) Khan, H. Y.; Çağır, Ali; Li, Y.; Kanbur, Tuğçe; Aboukameel, A.; Mpilla, G.; Sexton, R.; Kanbur, Tuğçe; Nagasaka, M.; Çetinkaya, Hakkı; Çağır, Ali; 04.01. Department of Chemistry; 01. Izmir Institute of Technology; 04. Faculty of Science
    Mutations in KRAS are among the most common aberrations in cancer. However, despite considerable research efforts, KRAS remains a challenging therapeutic target. In recent years, there has been a drive to develop KRAS mutant specific drugs. Among the different known mutations, the KRASG12C (glycine 12 to cysteine) has been considered druggable. Studies have shown that due in part to the close proximity of Cysteine 12 to both the nucleotide pocket and the switch regions, thiol-reactive compounds can bind to the active site covalently and inhibit KRASG12C mutation-driven signaling. The absence of this particular cysteine residue in wild-type KRAS makes such an approach very selective towards cancer cells.