Synthesis of new 2-aminothiazolyl/benzothiazolyl-based 3,4-dihydropyrimidinones and evaluation of their effects on adenocarcinoma gastric cell migration.
Mohsen SaghaFatemeh MousaeiMahtab SalahiNima Razzaghi-AslPublished in: Molecular diversity (2021)
Gastric cancer is one of the malignant tumors of the gastrointestinal tract that, despite its decrease in recent years, is still the fourth most common cancer and the second leading cause of cancer-related death. Various strategies including chemotherapy are used to keep cancer cells from spreading and induce apoptotic death in them. Recent studies have shown that dihydropyrimidinones (DHPMs) are privileged structures in medicinal chemistry due to their pharmacological effects. A number of new 2-aminothiazolyl/benzothiazolyl derivatives of 3,4-DHPMs (3-8) were synthesized and structurally identified, and then their effects on the migration behavior of human AGS cells (gastric cancer cells) were investigated. Molecular docking and molecular dynamics (MD) simulations were applied to explore binding potential and realistic binding model of the assessed derivatives through identification of key amino acid residues within L5/α2/α3 allosteric site of kinesin 5 (Eg5) as a validated microtubule-dependent target for monastrol as a privileged DHPM derivative.
Keyphrases
- molecular dynamics
- molecular docking
- cell migration
- papillary thyroid
- density functional theory
- squamous cell
- amino acid
- induced apoptosis
- endothelial cells
- cell death
- molecular dynamics simulations
- cell cycle arrest
- squamous cell carcinoma
- locally advanced
- small molecule
- climate change
- oxidative stress
- transcription factor
- childhood cancer
- endoplasmic reticulum stress
- structure activity relationship
- single molecule
- pluripotent stem cells
- radiation therapy
- atomic force microscopy
- risk assessment
- human health