Molecular design and synthesis of certain new quinoline derivatives having potential anticancer activity

EGFR, which plays a vital role as a regulator of cell growth, is one of the intensely studied TK targets of anticancer inhibitors. The most two common anticancer inhibitors are anilinoquiazolines and anilinoquinolines that inhibit EGFR kinase intracellularly. The present investigation dealt with des...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2015-09, Vol.102, p.115-131
Main Authors: Ibrahim, Diaa A., Abou El Ella, Dalal A., El-Motwally, Amira M., Aly, Rasha M.
Format: Article
Language:English
Subjects:
4-anilinoquinoline-3-carboxamide
Anti-proliferative activity
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Binding energy
Cell Proliferation - drug effects
Docking study
Dose-Response Relationship, Drug
Drug Design
Drug Screening Assays, Antitumor
EGFR-TK inhibitors
Humans
MCF-7 Cells
Molecular Structure
Pharmacophore
Protein Kinase Inhibitors - chemical synthesis
Protein Kinase Inhibitors - chemistry
Protein Kinase Inhibitors - pharmacology
Quinolines - chemistry
Quinolines - pharmacology
Receptor, Epidermal Growth Factor - antagonists & inhibitors
Receptor, Epidermal Growth Factor - metabolism
Structure-Activity Relationship
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Summary:EGFR, which plays a vital role as a regulator of cell growth, is one of the intensely studied TK targets of anticancer inhibitors. The most two common anticancer inhibitors are anilinoquiazolines and anilinoquinolines that inhibit EGFR kinase intracellularly. The present investigation dealt with design (pharmacophore, docking and binding energy) and synthesis of a new series of 4-anilinoquinoline-3-carboxamide derivatives as potential anticancer agents targeting EGFR. All the newly synthesized compounds were screened for their anticancer activity against MCF-7 and compounds 4f, 7a and 7b showed significant activity with IC50 values 13.96 μM, 2.16 μM and 3.46 μM, respectively. Most of the synthesized compounds were subjected to enzyme assay (EGFR TK) for measuring their inhibitory activity with the determination of IC50 values and the preliminary results revealed that compound 7b, which had potent inhibitory activity in tumor growth and had potent activity on the EGFR TK enzyme with 67% inhibition compared to ATP would be a potential anticancer agent. The present work explores the utility of 4-anilino quinolone-3-carboxamide, a privileged scaffold as inhibitors of protein kinases (EGFR) with high and selective anticancer activities. [Display omitted] •We use computer aided drug design to discover site-specific inhibitors for EGFR.•The proposed compounds were selecting due to their fit values, docking scores and binding energy.•The selected compounds were synthesized and changes in the side chains were studied to yield notable tumor activity.•The newly synthesized compounds were studies as EGFR inhibitors and as antitumor agents.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2015.07.030