A New 1,8-Naphthyridine-Pivalamide Hybrid: Synthesis, Structural Elucidation, Hirshfeld Surface Analysis, DFT Study, ADME Analysis and Molecular Docking Studies against EGFR and CDK6

This investigation focuses on the design, synthesis, comprehensive analysis and binding affinity with the epidermal growth factor receptor (EGFR), Cyclin-Dependent Kinase 6 (CDK6) of a new 1,8-naphthyridine-pivalamide hybrid 1. The newly synthesized 1,8-naphthyridine-pivalamide hybrid 1 was characterized by FT-IR, 1 H NMR, elemental analysis and single-crystal X-ray analysis. The crystal structure analysis disclosed that 1 is hydrated and supramolecular assembly is stabilized via O−H[Formula: see text]N, N−H[Formula: see text]O, and O−H[Formula: see text]O and off-set [Formula: see text] contacts. Various types of noncovalent contacts existing in the 1,8-naphthyridine-pivalamide hybrid 1 are explored, and subsequently quantified employing Hirshfeld surface analysis and 2D fingerprint plots. Furthermore, a void study was utilized to examine the mechanical stability and presence of the cavity within the solid-state structure of 1. The interaction energies between molecules in 1 have been investigated using the interaction energy calculation. Geometric parameters of the optimized structure of 1 were determined utilizing the DFT calculations. Furthermore, molecular docking studies indicated that the 1,8-naphthyridine-pivalamide hybrid 1 demonstrated promising binding affinity with EGFR and CDK6, compared to their known inhibitors. The newly synthesized 1,8-naphthyridine-pivalamide hybrid 1 also exhibited drug-likeness as predicted by SwissADME.