Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

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

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Citation - WoS: 8
Citation - Scopus: 9
Crm1 Inhibitory and Antiproliferative Activities of Novel 4'-alkyl Substituted Klavuzon Derivatives
(Elsevier Ltd., 2017) Kanbur, Tuğçe; Kara, Murat; Kutluer, Meltem; Şen, Ayhan; Delman, Murat; Alkan, Aylin; Otaş, Hasan Ozan; Akçok, İsmail; Çağır, Ali; 04.01. Department of Chemistry; 01. Izmir Institute of Technology; 04. Faculty of Science
Klavuzons are 6-(naphthalen-1-yl) substituted 5,6-dihydro-2H-pyran-2-one derivatives showing promising antiproliferative activities in variety of cancer cell lines. In this work, racemic syntheses of nine novel 4′-alkyl substituted klavuzon derivatives were completed in eight steps and anticancer properties of these compounds were evaluated. It is found that size of the substituent has dramatic effect over the potency and selectivity of the cytotoxic activity in cancerous and healthy pancreatic cell lines. The size of the substituent can also effect the CRM1 inhibitory properties of klavuzon derivatives. Strong cytotoxic activity and CRM1 inhibition can be observed only when a small substituent present at 4′-position of naphthalen-1-yl group. However, these substituents makes the molecule more cytotoxic in healthy pancreatic cells rather than cancerous pancreatic cells. Among the tested compounds 1,2,3,4-tetrahydrophenanthren-9-yl substituted lactone was the most cytotoxic compound and its antiproliferative activity was also tested in 3D spheroids generated from HuH-7 cell lines.
Citation - WoS: 10
Citation - Scopus: 11
A New Drug Testing Platform Based on 3d Tri-Culture in Lab-On Devices
(Elsevier, 2020) Gökçe, Begüm; Akçok, İsmail; 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.

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Browsing Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik by Subject "3D cell culture"