Quinazoline-oxadiazole hybrids: Synthesis, SC-XRD, Hirshfeld surface analysis and computational investigations

A novel series of twelve quinazoline-based oxadiazole hybrids was synthesized via a concise four-step synthetic route and comprehensively characterized by FTIR, ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry. Single crystal-XRD results confirmed that the para-fluoro-substituted derivative adopts a monoclinic crystal system and is assigned to the P2₁/c space group. The molecular structure featured a nearly coplanar arrangement of the oxadiazole and quinazoline rings, with a dihedral angle of 1.5°, while the fluorophenyl–oxadiazole linkage displayed a dihedral angle of 12.8°, suggesting slight torsional deviation. Hirshfeld surface analysis indicated that intermolecular contacts such as H···F (26.3 %), H···N (8.7 %), H···O (7.3 %), and π···π stacking interactions play a key role in molecular packing and lattice stability. Molecular docking studies were conducted to evaluate the interaction of the synthesized hybrids with histone deacetylase 7 (HDAC7), an epigenetic target implicated in oncogenesis. The docking analysis revealed favorable binding within the HDAC7 active site. Furthermore, a 100 ns molecular dynamics simulation revealed that the HDAC7–ligand complex maintained structural integrity, exhibited minimal RMSD deviations, and preserved key interactions throughout the simulation. ADME predictions using the QikProp module suggested favorable pharmacokinetic properties and drug-likeness. Collectively, the results offer comprehensive structural and computational insights into quinazoline–oxadiazole hybrids, providing a foundation for future biological evaluation.