Design, synthesis and assessment of new series of quinazolinone derivatives as EGFR inhibitors along with their cytotoxic evaluation against MCF7 and A549 cancer cell lines

Aziz, Marian W.; Kamal, Amr; Mohamed, Khaled O.

doi:10.1016/j.bmcl.2021.127987

Cited by 19 publications

(12 citation statements)

References 37 publications

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“…Apoptosis of A549 cells is an efficient route to clear out the extra cancer cells in the tissue homeostasis. It has been found that many drugs for EGFR could induce apoptosis of A549 cells 39 . Therefore, compound 4c was employed to investigate apoptosis against A549 cells.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluation of a series of dianilinopyrimidines as EGFR inhibitors

Yan

Wang

Liu

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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This paper described our efforts to develop dianilinopyrimidines as novel EGFR inhibitors. All the target compounds were tested for inhibitory effects against wild type EGFR (EGFR wt ) and three tumour cells, including A549, PC-3, and HepG2. Some of the compounds performed well in antitumor activities. Especially, compound 4c 2-((2-((4-(3-fluorobenzamido)phenyl)amino)-5-(trifluoromethyl) pyrimidin-4-yl)amino)- N -methylthiophene-3-carboxamide showed higher anti-tumour activities than Gefitinib. The IC 50 values of compound 4c against A549, PC-3, and HepG2. reached 0.56 μM, 2.46 μM, and 2.21 μM, respectively. In addition, further studies indicated that compound 4c could induce apoptosis against A549 cells and arrest A549 cells in the G2/M phase. Molecular docking studies showed that compound 4c could closely interact with EGFR. Generally, compound 4c was the potential for developing into an anti-tumour drug.

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Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluation of a series of dianilinopyrimidines as EGFR inhibitors

Yan

Wang

Liu

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…[27,31] Also, the replacement of a hydrogen atom at C-2 with a substituted phenyl ring reportedly showed significant efficacy toward several cancer cell lines, similar to EGFR-TKIs. [27,[31][32][33] Recent studies have validated 2,3-disubstituted quinazolinones as promising scaffolds for EGFR inhibition and NSCLC management (compounds A, B, and D), [23,34,35] and if substituted with bulkier hydrophobic groups at the 3-position, this could be advantageous. [23,25] Moreover, the addition of a lipophilic group at the 2-position has improved overall activity.…”

Section: Design Rationale For Egfr Inhibitorsmentioning

confidence: 99%

Quinazoline‐tethered hydrazone: A versatile scaffold toward dual anti‐TB and EGFR inhibition activities in NSCLC

Emam

Dahal

Singh

et al. 2021

Archiv der Pharmazie

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Globally, lung cancer and tuberculosis are considered to be very serious and complex diseases. Evidence suggests that chronic infection with tuberculosis (TB) can often lead to lung tumors; therefore, developing drugs that target both diseases is of great clinical significance. In our study, we designed and synthesized a suite of 14 new quinazolinones (5a-n) and performed biological investigations of these compounds in Mycobacterium tuberculosis (MTB) and cancer cell lines. In addition, we conducted a molecular modeling study to determine the mechanism of action of these compounds at the molecular level. Compounds that showed anticancer activity in the preliminary screening were further evaluated in three cancer cell lines (A549, Calu-3, and BT-474 cells) and characterized in an epidermal growth factor receptor (EGFR) binding assay. Cytotoxicity in noncancerous lung fibroblast cells was also evaluated to obtain safety data. Our theoretical and experimental studies indicated that our compounds showed a mechanism of action similar to that of erlotinib by inhibiting the EGFR tyrosine kinase. In turn, the antituberculosis activity of these compounds would be produced by the inhibition of enoyl-ACP-reductase. From our findings, we were able to identify two potential lead compounds (5i and 5l) with dual activity and elevated safety toward noncancerous lung fibroblast cells. In addition, our data identified three compounds with excellent anti-TB activities (compounds 5i, 5l, and 5n).

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“…10 Quinazolines as anticancer agents have received considerable attention since the development of the thymidylate synthetase inhibitors altitrexed and thymitaq. 11 Since then, several quinazolines have been described with anticancer activity, 10 among which the following can be highlighted: inhibitors of epidermal growth factor receptor (EGFR), 12 inhibitors of angiogenesis by inhibiting the vascular endothelial growth factor receptor (VEGFR-2) 13 and dihydrofolate reductase (DHFR) inhibitors that prevent the growth of cancer cells and depletes the cell from thymine causing cell death. 14 Consequently, DHFR inhibition played an essential role in medicine clinical as antitumor agents and becomes a target for the development of new antitumor agents.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, antitumor activity, 3D-QSAR and molecular docking studies of new iodinated 4-(3H)-quinazolinones 3N-substituted

et al. 2022

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Design, synthesis and assessment of new series of quinazolinone derivatives as EGFR inhibitors along with their cytotoxic evaluation against MCF7 and A549 cancer cell lines

Cited by 19 publications

References 37 publications

Design, synthesis and biological evaluation of a series of dianilinopyrimidines as EGFR inhibitors

Design, synthesis and biological evaluation of a series of dianilinopyrimidines as EGFR inhibitors

Quinazoline‐tethered hydrazone: A versatile scaffold toward dual anti‐TB and EGFR inhibition activities in NSCLC

Synthesis, antitumor activity, 3D-QSAR and molecular docking studies of new iodinated 4-(3H)-quinazolinones 3N-substituted

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