Crystal structure, Hirshfeld surface, DFT, mol-ecular docking of 1-[(6-tert-butyl-2-oxo-2H-chromen-4-yl)meth-yl]-4,4-di-methyl-piperidine-2,6-dione and cytotoxic effects on breast cancer (MDA-MB 231), human alveolar basal epithelial (A549) cell lines.

The title compound, C21H25NO4, was synthesized by SN2 reaction of bromo-methyl coumarin with 4,4-di-methyl-piperidine-2,6-dione. The mol-ecule crystalizes in the monoclinic system with space group C2/c. The coumarin unit is almost planar with a dihedral angle between the aromatic rings of 0.81 (2)° and an r.m.s deviation of 0.042 Å. The piperidine ring adopts a chair conformation with the two methyl groups, one methyl group occupying an axial position and the other an equatorial position, exhibiting maximum stability. In the crystal, C-H⋯O inter-actions lead to the formation of head-to-head dimers with an R 2 2(8)graph-set motif and R 2 1(9) and R 2 2(10) ring motifs along [001] and [100]. π-π inter-actions [centroid-centroid distances = 3.885 (2) and 3.744 (2) Å] are also observed. A Hirshfeld surface analysis was carried out, with the two-dimensional fingerprint plots indicating that the major contributions to the crystal packing are from H⋯H(57%), O⋯H(29.3%) and C⋯H(8.1%) inter-actions. The energy framework calculations reveal that dispersion energy (E dis= -267.7 kJ mol-1) dominates the other energies. The mol-ecular structure was optimized by density functional theory calculations using the B3LYP/6-311+G(d,p) basis set. The HOMO and LOMO orbitals were generated to determine the energy gap, which is 4.245 eV. Mol-ecular docking studies were carried out for the title mol-ecule as ligand and a protein as receptor giving binding affinities of -9.5 kcal mol-1 for PDB ID: 5HG8 and -8.2 kcal mol-1 for PDB ID:6 NLV. The compound was further subjected to biological studies against human cancer cell lines, namely cryopreserved triple negative human breast adenocarcinoma cells (MDA-MB-231cells) and adenocarcinomic human alveolar basal epithelial cells (A549 cells) giving IC50values of 11.57 and 9.34 µM, respectively. The cytotoxicity results showed a good safety profile against HEK293 cell lines.