Abstract
Background: Cancer is a major health problem to human beings around the world. Many quinazoline derivatives were reported to have potent cytotoxic activity.
Aims: Our aim in this work is the discovery of potent epidermal growth factor receptor (EGFR) inhibitors with anti-breast cancer activity containing 4-substituted quinazoline pharmacophore. Method: Novel series of 4-substituted 6,8-dibromo-2-(4-chlorophenyl)-quinazoline derivatives have been designed and synthesized. New derivatives were tested against MCF-7 (human breast carcinoma cell line) and screened for their inhibition activity against epidermal growth factor receptor tyrosine kinase (EGFR-TK). Result: Most of the tested compounds show potent antiproliferative activity and EGFR-TK inhibitory activity. Compounds VIIIc and VIIIb exerted powerful cytotoxic activity (IC50 3.1 and 6.3 μM) with potent inhibitory percent (91.1 and 88.4%) against EGFR-TK. Compounds IX, VIIa, X, VIIb, VIc, V, IV, VIa and VIb showed promising cytotoxic effects with IC50 range (12-79 μM) with good activity against EGFR-TK with the inhibitory percent (85.4-60.8%). On the other hand, compounds VIIc, VIIIa exerted low cytotoxic effects as revealed from their IC50 value (124 and 144 μM) with low activity against EGFR-TK with inhibitory percent 30.6 and 29.1% respectively.Keywords: Breast cancer, EGFR TK, IC50, quinazolines, synthesis, design.
Anti-Cancer Agents in Medicinal Chemistry
Title:Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity
Volume: 17 Issue: 6
Author(s): Marwa F. Ahmed*Naja Magdy
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo,Egypt
Keywords: Breast cancer, EGFR TK, IC50, quinazolines, synthesis, design.
Abstract: Background: Cancer is a major health problem to human beings around the world. Many quinazoline derivatives were reported to have potent cytotoxic activity.
Aims: Our aim in this work is the discovery of potent epidermal growth factor receptor (EGFR) inhibitors with anti-breast cancer activity containing 4-substituted quinazoline pharmacophore. Method: Novel series of 4-substituted 6,8-dibromo-2-(4-chlorophenyl)-quinazoline derivatives have been designed and synthesized. New derivatives were tested against MCF-7 (human breast carcinoma cell line) and screened for their inhibition activity against epidermal growth factor receptor tyrosine kinase (EGFR-TK). Result: Most of the tested compounds show potent antiproliferative activity and EGFR-TK inhibitory activity. Compounds VIIIc and VIIIb exerted powerful cytotoxic activity (IC50 3.1 and 6.3 μM) with potent inhibitory percent (91.1 and 88.4%) against EGFR-TK. Compounds IX, VIIa, X, VIIb, VIc, V, IV, VIa and VIb showed promising cytotoxic effects with IC50 range (12-79 μM) with good activity against EGFR-TK with the inhibitory percent (85.4-60.8%). On the other hand, compounds VIIc, VIIIa exerted low cytotoxic effects as revealed from their IC50 value (124 and 144 μM) with low activity against EGFR-TK with inhibitory percent 30.6 and 29.1% respectively.Export Options
About this article
Cite this article as:
Ahmed F. Marwa*, Magdy Naja, Design and Synthesis of 4-substituted Quinazolines as Potent EGFR Inhibitors with Anti-breast Cancer Activity, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (6) . https://dx.doi.org/10.2174/1871520616666160923103222
DOI https://dx.doi.org/10.2174/1871520616666160923103222 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Recent Advances in Herbal Nanomedicines for Cancer Treatment
Current Molecular Pharmacology The ATP-driven Hsp60 Machinery: Biological and Clinical Implications
Current Immunology Reviews (Discontinued) Novel Therapeutic Strategies for Dementia
CNS & Neurological Disorders - Drug Targets Reducing False Positive Findings in Statistical Analysis of Pharmacogenomic Biomarker Studies Using High-Throughput Technologies
Current Drug Safety Biomarkers of Angiogenesis and their Role in Patient Selection for Antiangiogenic Therapy
Current Angiogenesis (Discontinued) DNA Damage Response Pathways and Cell Cycle Checkpoints in Colorectal Cancer: Current Concepts and Future Perspectives for Targeted Treatment
Current Cancer Drug Targets Potential Role of Polyphenols in the Prevention of Cardiovascular Diseases: Molecular Bases
Current Medicinal Chemistry Targeted Therapy of Ovarian Cancer with Angiogenesis Inhibitors
Current Drug Targets Low Concentration of Caffeine Inhibits the Progression of the Hepatocellular Carcinoma <i>via Akt</i> Signaling Pathway
Anti-Cancer Agents in Medicinal Chemistry Arsenic trioxide Alters the MicroRNA Expression Profile of U87 glioblastoma
Anti-Cancer Agents in Medicinal Chemistry Antiestrogenic Therapies in Solid Cancers and Multiple Myeloma
Current Molecular Medicine Caring for HIV-Infected Patients in the ICU in The Highly Active Antiretroviral Therapy Era
Current HIV Research ROS-Responsive Nanomedicine: Towards Targeting the Breast Tumor Microenvironment
Current Medicinal Chemistry Hybrid Benzoxazole-Coumarin Compounds Induce Death Receptor-Mediated Switchable Apoptotic and Necroptotic Cell Death on HN-5 Head and Neck Cancer Cell Line
Anti-Cancer Agents in Medicinal Chemistry Oral and Intravenous Ibandronate in the Management of Postmenopausal Osteoporosis: A Comprehensive Review
Current Pharmaceutical Design Targeting of Nuclear Factor-κB and Proteasome by Dithiocarbamate Complexes with Metals
Current Pharmaceutical Design Cell Cycle Re-Entry in Alzheimers Disease: A Major Neuropathological Characteristic?
Current Alzheimer Research Use of Metformin and Survival of Diabetic Women with Breast Cancer
Current Drug Safety Image-Guided Drug Delivery with Single-Photon Emission Computed Tomography: A Review of Literature
Current Drug Targets Smell and Taste Disorders Resulting from Cancer and Chemotherapy
Current Pharmaceutical Design