Biological Evaluation of Novel Pyrazolotriazolopyrimidine Derivatives as Candidates of EGFR Inhibitors in Different Cancers

Ghunaim, Mariam Jamal (2017) Biological Evaluation of Novel Pyrazolotriazolopyrimidine Derivatives as Candidates of EGFR Inhibitors in Different Cancers. Masters thesis, الجامعة الإسلامية بغزة.

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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 Pyrazolotriazolopyrimidine derivatives especially BA-623 may hold potent anticancer effects. Keywords: Cancer, EGFR, biological activities, Pyrazolotriazolopyrimidine and tyrosine kinase inhibitors.

Item Type: Thesis (Masters)
Subjects: Q Science > QE Geology
Q Science > QR Microbiology
Depositing User: أ. دارين علي أحمد حمد
Date Deposited: 01 Mar 2021 11:59
Last Modified: 01 Mar 2021 11:59
URI: http://scholar.alaqsa.edu.ps/id/eprint/3895

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