Compounds Consisting of Quinazoline, Ibuprofen, and Amino Acids with Cytotoxic and Anti-Inflammatory Effects.
ChemMedChem
; 19(10): e202300651, 2024 May 17.
Article
in En
| MEDLINE
| ID: mdl-38354370
ABSTRACT
In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) and cyclooxygenase-2 (COX-2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A-431, MCF-7, MDA-MB-231) and epithelial non-tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC50) than gefitinib (reference drug) on three cancer cell lines (0.034â
µM in A-431, 2.67â
µM in MCF-7, and 3.64â
µM in AGS) without showing activity on the non-tumorigenic cell line (>100â
µM). Furthermore, assessment of EGFR-TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an inâ
vivo anti-inflammatory assay using the 12-O-tetradecanoylphorbol-3-acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR-TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX-2, involving S531. The RMSD graph indicated that the ligand remained stable in 50â
ns.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinazolines
/
Drug Screening Assays, Antitumor
/
Ibuprofen
/
Cyclooxygenase 2
/
ErbB Receptors
/
Amino Acids
/
Antineoplastic Agents
Language:
En
Journal:
ChemMedChem
Journal subject:
FARMACOLOGIA
/
QUIMICA
Year:
2024
Document type:
Article
Affiliation country:
México
Country of publication:
Alemania