Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

Permanent URI for this collectionhttps://hdl.handle.net/11147/9

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Author: search.filters.author.Çağır, AliDepartment: search.filters.department.İzmir Institute of Technology. Molecular Biology and Genetics

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Now showing 1 - 2 of 2
  • 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.
  • Article
    Citation - WoS: 10
    Citation - Scopus: 11
    A New Drug Testing Platform Based on 3d Tri-Culture in Lab-On Devices
    (Elsevier, 2020) Gökçe, Begüm; Çağır, Ali; Akçok, İsmail; Pesen Okvur, Devrim; Çağır, Ali; Pesen Okvur, Devrim; 04.03. Department of Molecular Biology and Genetics; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of Technology
    Drug discovery has a 90% rate of failure because preclinical platforms for drug testing do not mimic the in vivo conditions. Doxorubicin (DOX) is a commonly used drug to treat breast cancer patients even though it has side effects. Lab-on-a-chip (LOC) devices provide spatial control at the micrometer scale and can thus emulate the cancer microenvironment. Here, using a multidisciplinary approach, a new drug testing platform based on 3D tri-culture in LOC devices was developed. Breast cancer cells alone or with normal mammary epithelial cells and macrophages were cultured in matrigel in LOC devices. The platform was used to test DOX and (R)-4'-methylklavuzon (KLA), which is a new anti-cancer drug candidate. Results showed that DOX and KLA were equally effective on breast cancer cells in 3D monoculture. KLA produced 26% less death for breast cancer cells than DOX in 3D tri-culture. More importantly, DOX was not selective between breast cancer cells and normal mammary epithelial cells in 3D tri- culture whereas KLA caused 56% less cell death than DOX for normal mammary epithelial cells. Results strongly recommend that 3D tri-culture in LOC devices be used for assessment of drug toxicity at the preclinical stage.