Synthesis, in-Silico, drug-likeness studies, ADMET prediction and anticancer activity: novel 4-quinazolinyloxymethyl 3-aniline appended aryl amide derivatives

Quinazoline has become a significant scaffold in pharmaceutical chemistry due to its unusual bioactivity and versatile biological profile. In this study, a library of 4-quinazolinyloxymethyl-3-aniline amide derivatives (6a−6k) and (7a−7k) was synthesized and characterized by FT-IR, ¹H-NMR, and LC-MS. The anticancer activity of newly synthesized molecules was investigated on cancer cell lines MCF-7 and A549. Molecular docking studies (PDB ID: 3VHE) were performed on all synthesized targeted compounds and on the standard drug. All compounds showed better interactions than sorafenib, except 6i and 7i. ADMET studies showed no Ames toxicity and obeyed Lipinski’s rule of five. The stability of the molecular docking results over time was investigated using 100 ns molecular dynamics simulations. Molecular dynamics simulations demonstrated that the 7k targeted molecule remained stable after docking to the binding sites of VEGFR2 receptors, with negligible conformational changes and oscillations.