Five Schiff bases, 2-((3-chlorophenylimino)methyl)-5-(diethylamino)phenol (L1), 2-((2,4-dichlorophenylimino)methyl)-5-(diethylamino)phenol (L2), 5-(diethylamino)-2-((3,5-dimethylphenylimino)methyl)phenol (L3), 2-((2-chloro-4-methylphenylimino)methyl)-5-(diethylamino)phenol (L4), and 5-(diethylamino)-2-((2,6-diethylphenylimino)methyl)phenol (L5) were synthesized and characterized by elemental analysis, FT-IR, ¹H and ¹³C NMR spectroscopy. Three of the compounds (L1, L2, and L4) were analyzed by single crystal X-ray diffraction: L1 and L2 crystallized in orthorhombic P2₁2₁2₁ and Pca2₁ space group, respectively, while L4 crystallized in monoclinic P2₁/c space group. Theoretical investigations were performed for all the synthesized compounds to evaluate the structural details. Drug–DNA interaction studies results from UV–Vis spectroscopy and electrochemistry complement that the compounds bind to DNA through electrostatic interactions. The cytotoxicity of the synthesized compounds was studied against cancer cell lines (HeLa and MCF-7) and a normal cell line (BHK-21) by means of an MTT assay compared to carboplatin, featuring IC₅₀ values in the micromolar range. The pro-apoptotic mechanism for the active compound L5 was evaluated by fluorescence microscopy, cell cycle analysis, caspase-9 and -3 activity, reactive oxygen species production, and DNA binding studies that further strengthen the results of that L5 is a potent drug against cancer. Communicated by Ramaswamy H. Sarma

NIMA related Kinases (NEK7) plays an important role in spindle assembly and mitotic division of the cell. Over expression of NEK7 leads to the progression of different cancers and associated malignancies. It is becoming the next wave of targets for the development of selective and potent anti-cancerous agents. The current study is the first comprehensive computational approach to identify potent inhibitors of NEK7 protein. For this purpose, previously identified anti-inflammatory compound i.e., Phenylcarbamoylpiperidine-1,2,4-triazole amide derivatives by our own group were selected for their anti-cancer potential via detailed Computational studies. Initially, the density functional theory (DFT) calculations were carried out using Gaussian 09 software which provided information about the compounds' stability and reactivity. Furthermore, Autodock suite and Molecular Operating Environment (MOE) software’s were used to dock the ligand database into the active pocket of the NEK7 protein. Both software performances were compared in terms of sampling power and scoring power. During the analysis, Autodock results were found to be more reproducible, implying that this software outperforms the MOE. The majority of the compounds, including M7, and M12 showed excellent binding energies and formed stable protein–ligand complexes with docking scores of − 29.66 kJ/mol and − 31.38 kJ/mol, respectively. The results were validated by molecular dynamics simulation studies where the stability and conformational transformation of the best protein–ligand complex were justified on the basis of RMSD and RMSF trajectory analysis. The drug likeness properties and toxicity profile of all compounds were determined by ADMETlab 2.0. Furthermore, the anticancer potential of the potent compounds were confirmed by cell viability (MTT) assay. This study suggested that selected compounds can be further investigated at molecular level and evaluated for cancer treatment and associated malignancies.