Design and Synthesis of Trisubstituted Pyrimidine Derivatives as Coactivator Binding Inhibitors (CBIs) of Estrogen Receptor Signaling

الموضوعات

طب

الملخص

Breast cancer (BC) is one of the most commonly diagnosed cancers in women. Estrogen signalingand the estrogen receptors (ERα, ERβ) are implicated in breast cancer progression. Majority ofbreast 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 ERactivity and arrest the estrogen-dependent growth of BC still represents the primary treatment forbreast cancer patients. This approach, however, frequently fails and patients develop resistant breastcancer, which is almost untreatable. In this project we focused on synthesizing a potent coactivatorbinding inhibitors (CBIs) molecules that block ER activity through a different mechanism that mayarrest the estrogen-dependent growth of BC and offer a solution to the existing resistance. Coactivatorbinding inhibitors (CBIs) act by blocking the conformational change needed for DNAbinding and gene expression. In this project set of compounds have been designed, synthesizedthrough sequential substitution of the chlorine atoms of 2,4,6-trichloropyrimidine with amines orother nucleophiles. The synthesized compounds were purified using chromatography techniques,and characterized by (1H-NMR, 13C-NMR, FT-IR and MS (ESI)) spectroscopy. Some of thesecompounds 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 casecells 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 potentactivities against the two forms of Molm-13 cell lines and have a dose dependent effect while thecompound MY2 (25) showed no significant inhibitory action on the same cell lines.

روابط وملفات

التعريف والنوع

رقم الوثيقة

f62c7b70-1361-463a-98f8-3e442c795317

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

1696925_1.pdf

بيانات النشر

ترجمة العنوان

تصميم و تحضير مشتقات البيريميدين ثلاثية التفرع كمثبطات لبروتين مرافق المنشط لمستقبلات الاستروجين

ألقاب المؤلفين

[{"name_ar":"ميران محمد جمال طلال مسودى","title_ar":"اعداد","title_en":"Preparation"},{"name_ar":"يوسف نجاجرة","title_ar":"اشراف","title_en":"Supervision"}]

اللغة

English

المصدر والدورية

اسم المصدر

Design and Synthesis of Trisubstituted Pyrimidine Derivatives as Coactivator Binding Inhibitors (CBIs) of Estrogen Receptor Signaling

المحتوى والصفحات

عدد الصفحات

0

إشراف وإعداد

الإشراف

يوسف نجاجرة

الإعداد

ميران محمد جمال طلال مسودى

الاقتباسات الببليوغرافية