تصميم و تحضير مشتقات البيريميدين ثلاثية التفرع كمثبطات لبروتين مرافق المنشط لمستقبلات الاستروجين Design and Synthesis of Trisubstituted Pyrimidine Derivatives as Coactivator Binding Inhibitors (CBIs) of Estrogen Receptor Signaling

dc.contributor.advisor يوسف نجاجرة
dc.contributor.author ميران محمد جمال طلال مسودى ar
dc.contributor.author Miran M.Jamal Talal Masswadeh en
dc.contributor.examiner Zaidoun Salah
dc.contributor.examiner Tawfeq Kaimari
dc.date.accessioned 2018-10-07T11:30:52Z
dc.date.available 2018-10-07T11:30:52Z
dc.date.issued 2016-01-09
dc.description.abstract Breast cancer (BC) is one of the most commonly diagnosed cancers in women. Estrogen signaling and the estrogen receptors (ERα, ERβ) are implicated in breast cancer progression. Majority of breast cancers start out as estrogen dependent as a result of overexpression of ER-regulated genes: Estrogen deprivation therapy using anti-estrogens (AEs) and aromatase inhibitors (AIs) to block ER activity and arrest the estrogen-dependent growth of BC still represents the primary treatment for breast cancer patients. This approach, however, frequently fails and patients develop resistant breast cancer, which is almost untreatable. In this project we focused on synthesizing a potent coactivator binding inhibitors (CBIs) molecules that block ER activity through a different mechanism that may arrest the estrogen-dependent growth of BC and offer a solution to the existing resistance. Coactivator binding inhibitors (CBIs) act by blocking the conformational change needed for DNA binding and gene expression. In this project set of compounds have been designed, synthesized through sequential substitution of the chlorine atoms of 2,4,6-trichloropyrimidine with amines or other nucleophiles. The synthesized compounds were purified using chromatography techniques, and characterized by (1H-NMR, 13C-NMR, FT-IR and MS (ESI)) spectroscopy. Some of these compounds were screened for their inhibitory activity against the acute myeloid leukemia cells (Molm-13) cells. Two forms of Molm-13 had been used to evaluate the role of p53. In one case cells were transfected with empty vector and in the other the cells were tranfected with sh-p53 RNA(sh-p53). The viability of cells was determined using WST-1 assay. Initial results of the tested compounds demonstrated that MY12 (35) and MY3 (26) exhibited potent activities against the two forms of Molm-13 cell lines and have a dose dependent effect while the compound MY2 (25) showed no significant inhibitory action on the same cell lines. en
dc.identifier.other 21112816
dc.identifier.uri https://dspace.alquds.edu/handle/20.500.12213/1321
dc.language.iso en_US
dc.publisher AL-Quds University en
dc.publisher جامعة القدس ar
dc.subject العلوم الصيدلانية ar
dc.subject Pharmaceutical Sciences en
dc.subject.other رسالة ماجستير ar
dc.subject.other دراسات عليا ar
dc.subject.other Higher Studies en
dc.subject.other Master Thesis en
dc.title تصميم و تحضير مشتقات البيريميدين ثلاثية التفرع كمثبطات لبروتين مرافق المنشط لمستقبلات الاستروجين ar
dc.title Design and Synthesis of Trisubstituted Pyrimidine Derivatives as Coactivator Binding Inhibitors (CBIs) of Estrogen Receptor Signaling en
dc.type Thesis
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