Efficient synthesis and antitumor activity of novel oxazaphosphinane derivatives: X-ray crystallography, DFT study and molecular docking.
Rania BahadiMalika BerredjemBillel BelhaniSeif-Eddine DjouadSofiane BouacidaTan Sothea OukYacine LaichiKhaldoun BachariRayenne RedjemiaPublished in: Journal of biomolecular structure & dynamics (2022)
A novel potentially biologically active oxazaphosphinane derivatives was synthesized by facile synthetic approaches from the combination of hydroxyaniline, aldehyde, and triethylphosphite. The crystal structure of compound 1b has been determined. Single crystals belong to the triclinic system with p - 1 space. The relative in vitro antitumor activity against human cell lines (PRI, K562, and JURKAT) of these derivatives in comparison to chlorombucil is reported. All synthesized compound showed excellent activity with IC50 value of 0.014-0.035 mM. The binding energy of the Epidermal growth factor receptor (EGFR)-oxazaphosphinane complex and the calculated inhibition constant using docking simulation showed that all molecules has the ability to inhibit EGFR therapeutic target. In addition, DFT calculation has been used to analyze the electronic and geometric characteristics.
Keyphrases
- epidermal growth factor receptor
- molecular docking
- molecular dynamics simulations
- tyrosine kinase
- advanced non small cell lung cancer
- endothelial cells
- small cell lung cancer
- structure activity relationship
- molecular dynamics
- density functional theory
- high resolution
- magnetic resonance
- induced pluripotent stem cells
- quantum dots
- magnetic resonance imaging
- binding protein
- protein protein
- reduced graphene oxide
- oxide nanoparticles
- transcription factor