Studies directed towards The synthesis Of İmatinib Mesylate ((Gleevec), 4-(4-Methyl-Piperazin-1- Ylmethyl)-N-[4- Methyl-3-(4-Pyridin-3-Yl-Pyrimidin-2- Ylamino)-Phenyl]- Benzamide Methanesulfonate) Analogs

Günay, Neşet Batuhan
Imatinib mesylate is indicated for the treatment of chronic myeloid leukemia (CML) and unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). By the application of this anticancer drug, problems occurs in terms of stability and activity. Computer assisted design (CAD) works showed that the modification of the B and C part molecule can increase the effectivity of the drug. The new derivatives of the drug will be obtained to change some part of the B and C segments. The total synthesis of a new imatinib mesylate will be done and the activity tests are going to be determined in collaboration with other groups.


Multidrug resistance mechanisms in imatinib resistant human chronic myeloid leukemia cells
Baran, Yusuf; Gündüz, Ufuk; Department of Biology (2006)
In this study, mechanisms of resistance to Imatinib-induced apoptosis in human K562 and Meg-1 chronic myeloid leukemia (CML) cells were examined. Continuous exposure of cells to step-wise increasing concentrations of Imatinib resulted in the selection of 0.2 and 1 ́M İmatinib resistant cells. Measurement of endogenous ceramide levels showed that treatment with Imatinib increased the generation of C18-ceramide significantly, which is mainly synthesized by the human longevity assurance gene 1 (hLASS1), in sen...
The low frequency of defective TPMT alleles in Turkish population: A study on pediatric patients with acute lymphoblastic leukemia
Tumer, Tugba Boyunegmez; Ulusoy, Gulen; Adalı, Orhan; Sahin, Gurses; Gozdasoglu, Sevgi; Arinc, Ennel (Wiley, 2007-10-01)
6-Mercaptopurine (6MP) is an essential anticancer drug used in the treatment of childhood acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe toxicity or efficacy of 6MP Four variant alleles, TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C, are responsible over the 80% of low or undetectable enzyme activity. The frequencies of these variants were investigated among 106 children with ALL in Turkish population. TPM...
Efficient synthesis of novel near ir emitting distyrylboradiazaindacene sensitizers for photodynamic therapy
Dost, Zeynep; Akkaya, Engin Umut; Department of Chemistry (2006)
Photodynamic therapy (PDT) is a noninvasive method of treating malignant tumors and age-related macular degeneration. Current practice of PDT is limited to a few functionalized porphyrins, however these compounds are not considered to be ideal drugs for use in PDT. Among the limitations, the most prominent is the low extinction coefficient of porphyrins in the body’s therapeutic window. Therefore, there is a significant impetus to develop novel and better efficiency sensitizers for use in PDT. Boradiazainda...
Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death
Lee, Eric A.; Angka, Leonard; Rota, Sarah-Grace; Hanlon, Thomas; Mitchell, Andrew; Hurren, Rose; Wang, Xiao Ming; Gronda, Marcela; Boyacı, Ezel; Bojko, Barbara; Minden, Mark; Sriskanthadevan, Shrivani; Datti, Alessandro; Wrana, Jeffery L.; Edginton, Andrea; Pawliszyn, Janusz; Joseph, Jamie W.; Quadrilatero, Joe; Schimmer, Aaron D.; Spagnuolo, Paul A. (2015-06-15)
Treatment regimens for acute myeloid leukemia (AML) continue to offer weak clinical outcomes. Through a high-throughput cell-based screen, we identified avocatin B, a lipid derived from avocado fruit, as a novel compound with cytotoxic activity in AML. Avocatin B reduced human primary AML cell viability without effect on normal peripheral blood stem cells. Functional stem cell assays demonstrated selectivity toward AML progenitor and stem cells without effects on normal hematopoietic stem cells. Mechanistic...
Anti-Cancer Effects of Clofazimine As a Single Agent and in Combination with Cisplatin in Multiple Myeloma
Durusu, Ipek; Hüsnügil, Hepşen Hazal; Atas, Heval; Biber, Aysenur; Gerekci, Selin; Gulec, Aliye Ezgi; Özen, Can (2016-12-02)
Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high morbidity. Clofazimine (CLF) is an FDA-approved leprostatic, anti-tuberculosis, and anti-inflammatory drug that was previously shown to have growth suppression effect on various cancer types such as hepatocellular, lung, cervix, esophageal, colon, and breast cancer as well as melanoma, neuroblastoma, and leukemia. The objective of this study was to evaluate the anticancer effect and mechanism of CLF on U266 MM cell line. C...
Citation Formats
N. B. Günay, “Studies directed towards The synthesis Of İmatinib Mesylate ((Gleevec), 4-(4-Methyl-Piperazin-1- Ylmethyl)-N-[4- Methyl-3-(4-Pyridin-3-Yl-Pyrimidin-2- Ylamino)-Phenyl]- Benzamide Methanesulfonate) Analogs,” M.S. - Master of Science, Middle East Technical University, 2008.