Biological evaluation of novel Pyrazolotriazolopyrimidine derivatives as candidates of EGFR inhibitors in different cancers
Other Title(s)
التقييم البيولوجي لمثبطات جديدة لمستقبلات عامل النمو الطلائي (EGFR) في أنواع مختلفة من السرطان
Dissertant
Ghunaym, Maryam Jamal Muhammad
Thesis advisor
University
Islamic University
Faculty
Faculty of Science
Department
Department of Biological Science
University Country
Palestine (Gaza Strip)
Degree
Master
Degree Date
2017
English Abstract
Background: Cancer is one of the most serious diseases and represents a major threat to human health all over the world.
Epidermal growth factor receptors (EGFRs) have been shown to be implicated in tumour initiation and progression.
Despite of the important progress in EGFR inhibitors synthesis, many cancers develop resistance to these drugs.
Therefore, more effective EGFR tyrosine kinase inhibitors are required for cancer treatment.
Objective: This study has been conducted to evaluate the biological activities of a series of novel Pyrazolotriazolopyrimidine derivatives (BA623, BA642, BA645) compounds that have been synthesized as potential epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in human breast (MCF7), cervical (HELA) and colorectal (Caco-2) cancer.
Methods: MTT assay has been employed to evaluate the general toxicity of these compounds in the indicated cancer cells.
The anti-cancer effects of these compounds against cancer cells were assessed using trypan blue assay, growth curve and migration assay.
To understand the mechanism of action of the most promising Pyrazolotriazolopyrimidine (BA) compound, western blotting analysis and flow cytometry were performed.
Results: The results show significant toxicity of all three Pyrazolotriazolopyrimidine compounds tested in this study in a time and concentration dependent manner.
The toxicity of these compounds includes proliferation inhibition and cell death.
Importantly, these compounds showed a significant anti migration effect on HELA cells.
Of the tested compounds BA-623 has the most potent cytotoxic effect and we show here that this compound is able to inhibit EGFR/Akt signaling pathway resulting in activating p53 and p21 leading to G1 cell cycle arrest in MDA-MB-231 breast cancer cell line.
Conclusion: These results suggest that the tested Pyrazolotri
Main Subjects
No. of Pages
82
Table of Contents
Table of contents.
Abstract.
Abstract in Arabic.
Chapter One : Introduction.
Chapter Two : Literature review.
Chapter Three : Materials and methods.
Chapter Four : Results.
Chapter Five : Discussion.
Chapter Six : Conclusions and recommendations.
References.
American Psychological Association (APA)
Ghunaym, Maryam Jamal Muhammad. (2017). Biological evaluation of novel Pyrazolotriazolopyrimidine derivatives as candidates of EGFR inhibitors in different cancers. (Master's theses Theses and Dissertations Master). Islamic University, Palestine (Gaza Strip)
https://search.emarefa.net/detail/BIM-900924
Modern Language Association (MLA)
Ghunaym, Maryam Jamal Muhammad. Biological evaluation of novel Pyrazolotriazolopyrimidine derivatives as candidates of EGFR inhibitors in different cancers. (Master's theses Theses and Dissertations Master). Islamic University. (2017).
https://search.emarefa.net/detail/BIM-900924
American Medical Association (AMA)
Ghunaym, Maryam Jamal Muhammad. (2017). Biological evaluation of novel Pyrazolotriazolopyrimidine derivatives as candidates of EGFR inhibitors in different cancers. (Master's theses Theses and Dissertations Master). Islamic University, Palestine (Gaza Strip)
https://search.emarefa.net/detail/BIM-900924
Language
English
Data Type
Arab Theses
Record ID
BIM-900924
