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الرئيسية > Optimization of Synthetic Flav...>الوصف

Optimization of Synthetic Flavonolignans to Target Embryonic Signaling in Metastatic Ovarian and Colon Cancer

المؤلف الرئيسي: Amawi, Haneen (Author)
مؤلفين آخرين: Tiwari, Amit K. (Advisor)
التاريخ الميلادي: 2017
موقع: توليدو
الصفحات: 1 - 354
رقم MD: 999428
نوع المحتوى: رسائل جامعية
اللغة: الإنجليزية
الدرجة العلمية: رسالة دكتوراه
الجامعة: University of Toledo
الكلية: The Graduate Faculty
الدولة: الولايات المتحدة الأمريكية
قواعد المعلومات: +Dissertations
مواضيع:
العلوم الطبية | مركبات الفلافونوليجان | الأمراض السرطانية | سرطان المبيض | سرطان القولون
رابط المحتوى:
صفحة العنوان     
المستخلص     
قائمة المحتويات     
24 صفحة الأولى     

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المستخلص: This thesis work reports the synthesis and anticancer activity evaluation of twelve novel silybin analogues designed using a novel ring disjunctive based natural product lead (RDNPL) optimization approach. The twelve synthetic novel derivatives (HM015a- HM015k) were screened for their cytotoxicities against several cancerous cell lines and normal epithelial cells. HM015k or 15k, was selected as a leading compound where it induced potent and selective cytotoxicity against both ovarian (OV2008, A2780) and colon (HCT116, S, and LOVO) cancer cell lines. The cytotoxicity of 15k was further confirmed and 15k treatment induced significant inhibition in the cancer cells proliferation with time and their colony formation rates. Mechanistic studies indicated that the antiproliferative efficacy of 15k was mediated through significant induction of cell cycle arrest, oxidative stress, and apoptosis. Furthermore, 15k inhibited cellular microtubules dynamic and assembly by binding to tubulin and inhibiting its levels and function in both colon and ovarian cancer cells. The compound 15k reversed cancer cells migration and invasion potentials. Further, the 15k treatment induced significant reversal in EMT morphology and markers with significant downregulation in Wnt/ B-catenin signaling in both cancers. Finally, 15k was safe in zebrafish in vivo model at concentrations up to 10 μM and induced no cardiac or morphological toxicities.

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