scholarly journals 6,7-Disubstituted-4-anilinoquinazoline: Design, Synthesis and Anticancer Activity as a Novel Series of Potent Anticancer Agents

2020 ◽  
Vol 27 (2) ◽  
pp. 209-218
Author(s):  
Fatemeh Azmian Moghadam ◽  
Mehdi Evazalipour ◽  
Hassan Kefayati ◽  
Saeed Ghasemi
Keyword(s):  
Growth Factor ◽  
Anticancer Agents ◽  
Growth Factor Receptor ◽  
Docking Studies ◽  
Anticancer Activities ◽  
Design Synthesis ◽  
Atp Binding Site ◽  
Novel Approach ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Background: Epidermal Growth Factor Receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are responsible for several pathological conditions such as the development of different kinds of tumors. The combined inhibition of both signal transduction pathways seems to be a promising novel approach for cancer treatment. Methods: In this study, novel 4-anilinoquinazoline derivatives with various substituents on-7 position of quinazoline moiety were designed, synthesized, and evaluated for their antiproliferative activity against A431 and HU02 cell lines. Results: Compounds 8a, 8d, and 8f displayed the most potent anticancer activities against A431(IC50 = 1.78 μM, 8.25 μM, and 7.18 μM, respectively) in comparison with reference standards(erlotinib IC50=8.31 μM and vandetanib IC50=10.62 μM). Molecular docking studies proved that8a as the most potent compound could be efficiently accommodated in the ATP binding site ofEGFR and VEGFR-2 through the formation of essential hydrogen bonds between quinazolineN1 atom and the Met796 backbone of EGFR as well as the Cys919 backbone of VEGFR-2 with a distance of 1.94 Å and 1.398 Å, respectively. Conclusion: Compound 8a as the most potent compound with morpholine and 3-bromoaniline at the 7 and 4 positions of quinazoline scaffold, respectively, deserves more study and structural optimization as an anticancer agent.

scholarly journals Design, Synthesis and Evaluation of Core Scaffold Pyrazolone Fused Thiazolidinone Derivatives as Anticancer Agents

2021 ◽  
pp. 217-227
Author(s):  
Sumathy Arunachalam ◽  
Suresh Ramalingam ◽  
Gowrishankar Narayanasamy Lachmanan ◽  
Srinivasan Nagarajan
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Anticancer Agents ◽  
Growth Factor Receptor ◽  
Breast Carcinoma Cell Line ◽  
Design Synthesis ◽  
Standard Drug ◽  
Epidermal Growth

Background: Cancer is the world's second leading cause of death, accounting for an estimate of more than 10 million deaths annually. The most common type of cancers in women are breast, endometrial, cervical, ovarian, colorectal, lung, and skin cancers.Among these, breast cancer is the most common in women of all ages. Human epidermal growth factor receptor 2 breast cancer is widely seen in women which test positive for the protein HER2. This protein is present in one-fifth of every breast cancer cell, which promotes the growth of cancer cells. There are several compounds available for the treatment of HER2 breast cancer in the market with varying promise in their efficacy and safety on HER2 treatment. Objective: To design synthesis and evaluation of core scaffold pyrazolone fused thiazolidinone derivatives as anticancer agents. Methods: In this study, the core scaffold pyrazolone fused thiazolidinone derivatives were designed, synthesized, and analyzed for the anticancer activity using breast carcinoma cell line (MCF-7), against the standard drug Doxorubicin. Results: Many thiazoles, fused thiazole, and pyrazole derivatives have been found to have anti-cancer and other properties. In this study, the compound 1-phenyl-3-methyl-5-pyrazolones was allowed to react with diverse benzoyl chloride as well as primary amine derivatives and transformed into ’A series of Pyrazolone fused Thiazolidinone derivatives 4A1-4A10 and 4B1- 4B10. Computational studies by Schrodinger Glide XP using the Protein 3RCD which act on the human epidermal growth factor receptor’’ was performed on the selected scheme initially and further from the docked score data the synthesis of pyrazolone fused thiazolidinone was performed. Conclusion: Among the compounds synthesized, five compounds (4A6 − 3.4 kcal/mol, 4B4 − 3.0 kcal/mol, 4A3 − 2.2 kcal/mol, 4B2 − 1.6 kcal/mol, and 4A9 − 1.3 kcal/mol) shown promising binding affinities against epidermal growth factor receptor kinase. The cytotoxic potential of the compounds was examined using a breast carcinoma cell line (MCF-7), which shown cytotoxicity close to Doxorubicin (standard drug). Our findings are an important step forward in the development of novel anticancer agents.

scholarly journals A High-Content Biosensor-Based Screen Identifies Cell-Permeable Activators and Inhibitors of EGFR Function

2012 ◽  
Vol 17 (7) ◽  
pp. 885-899 ◽  
Author(s):  
Christophe Antczak ◽  
Jeni P. Mahida ◽  
Bhavneet Bhinder ◽  
Paul A. Calder ◽  
Hakim Djaballah
Keyword(s):  
Growth Factor ◽  
High Throughput Screening ◽  
Kinase Inhibitors ◽  
Signal To Noise Ratio ◽  
Growth Factor Receptor ◽  
Live Cells ◽  
Attrition Rates ◽  
Novel Approach ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Early success of kinase inhibitors has validated their use as drugs. However, discovery efforts have also suffered from high attrition rates due to lack of cellular activity. We reasoned that screening for such candidates in live cells would identify novel cell-permeable modulators for development. For this purpose, we have used our recently optimized epidermal growth factor receptor (EGFR) biosensor assay to screen for modulators of EGFR activity. Here, we report on its validation under high-throughput screening (HTS) conditions displaying a signal-to-noise ratio of 21 and a Z′ value of 0.56—attributes of a robust cell-based assay. We performed a pilot screen against a library of 6912 compounds demonstrating good reproducibility and identifying 82 inhibitors and 66 activators with initial hit rates of 1.2% and 0.95%, respectively. Follow-up dose-response studies revealed that 12 of the 13 known EGFR inhibitors in the library were confirmed as hits. ZM-306416, a vascular endothelial growth factor receptor (VEGFR) antagonist, was identified as a potent inhibitor of EGFR function. Flurandrenolide, beclomethasone, and ebastine were confirmed as activators of EGFR function. Taken together, our results validate this novel approach and demonstrate its utility in the discovery of novel kinase modulators with potential use in the clinic.

Fortgeschrittenes medulläres Schilddrüsenkarzinom: Vandetanib verbessert das progressionsfreie Überleben

2012 ◽  
Vol 03 (02) ◽  
pp. 93-92
Author(s):  
Alexander Kretzschmar
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
Vascular Endothelial ◽  
Medulläres Schilddrüsenkarzinom ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

Vandetanib ist ein oraler Hemmer des RET-Kinase-, VEGF (Vascular Endothelial Growth Factor Receptor)- und EGFR (Epidermal Growth Factor Receptor)-Signalwegs. In einer zulassungsrelevanten, randomisierten, doppelblinden, placebokontrollierten Phase- III-Studie verlängerte der Tyrosinkinasehemmer das progressionsfreie Überleben (PFS) signifikant länger als Placebo.

scholarly journals Long-term remission of a Her2/neu positive primary breast cancer under double monoclonal antibody therapy with trastuzumab and bevacizumab

2014 ◽  
Vol 48 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Robert Königsberg ◽  
Julia Maierhofer ◽  
Tanja Steininger ◽  
Gabriele Kienzer ◽  
Christian Dittrich
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Growth Factor ◽  
Antibody Therapy ◽  
Growth Factor Receptor ◽  
Over Expression ◽  
Single Target ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

AbstractBackground. The attempt to act on several signalling pathways involved in tumour development simultaneously appears to be more attractive than attacking a single target structure alone. Vascular endothelial growth factor (VEGF) over-expression is frequently observed in human epidermal growth factor receptor 2 (Her2/neu) positive patients with breast cancer and over-expression of the proto-oncogene Her2/neu is associated with an up-regulation of VEGF.Case report. The case of a Her2/neu positive patient with breast cancer who refused cytotoxic chemotherapy with its potential side effects as well as mastectomy is presented. Our patient has been receiving the combined double administration of bevacizumab and trastuzumab for more than 4 years.Conclusions. This case report shows that (a) the combined double administration of bevacizumab and trastuzumab was be clinically effective. (b) The combination of bevacizumab and trastuzumab is safe and non-toxic. (c) Bevacizumab and trastuzumab can be used as a long-term application

Dual inhibitors of epidermal growth factor receptor and topoisomerase IIα derived from a quinoline scaffold

RSC Advances ◽  
2016 ◽  
Vol 6 (81) ◽  
pp. 77717-77734 ◽  
Author(s):  
Monika Chauhan ◽  
Gaurav Joshi ◽  
Harveen Kler ◽  
Archana Kashyap ◽  
Suyog M. Amrutkar ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Anticancer Activities ◽  
Topoisomerase Iiα ◽  
Dual Inhibitors ◽  
Epidermal Growth ◽  
Egfr Kinase

Based on the quinazoline bearing EGFR inhibitors, a series of thirty four compounds having a quinoline scaffold were synthesized and evaluated in vitro for EGFR kinase inhibitory and anticancer activities.

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