Quinazoline based 1,3,5-triazine derivatives as cancer inhibitors by impeding the phosphorylated RET tyrosine kinase pathway: Design, synthesis, docking, and QSAR study.
Prateek PathakVladislav NaumovichMaria A GrishinaParjanya Kumar ShuklaAmita VermaVladimir A PotemkinPublished in: Archiv der Pharmazie (2019)
The present research focused on designing a quinazoline skeleton, framed via 1,3,5-triazine derivatives (QBT) through field mapping and alignment studies. The QBT derivatives were synthesized via time- and cost-effective protocol. The 3D-QSAR study, computational physicochemical properties, and ADME calculation of the derivatives were performed to establish the affinity towards the biological system. Molecular docking in the adenosine triphosphate binding site of the RET tyrosine kinase domain (PDB ID: 7IVU) was studied to elucidate vital structural residues necessary for bioactivity. The derivatives were evaluated for anticancer potency against TPC-1 cells (thyroid cancer), MCF-7 cells (breast cancer), and one normal cell line (human foreskin fibroblasts) via 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide assay followed by an in ovo CAM assay. The entire series of derivatives (8a-o) showed mild to significant anticancer potency against the selected cancer cell lines.
Keyphrases
- molecular docking
- tyrosine kinase
- structure activity relationship
- epidermal growth factor receptor
- molecular dynamics simulations
- induced apoptosis
- papillary thyroid
- molecular dynamics
- cell cycle arrest
- high throughput
- high resolution
- randomized controlled trial
- endothelial cells
- squamous cell
- small molecule
- childhood cancer
- high density
- extracellular matrix
- liquid chromatography
- protein protein
- simultaneous determination
- solid phase extraction
- protein kinase