In present work, new Schiff-base ligand, N-2-(6-methylpyridyl)-2-hydroxy- 1-naphthaldimine (1) and its Ni(II) complex, bis[N-2-(6-methylpyridyl)-2-oxo-1- naphthaldimnato-k3N^N^O] nickel(II) (2) have been reported and characterized by spectral techniques (IR, 1H NMR, Mass). Solid state structures and non-covalent interactions have great effect on the stability of the final structures. X-ray diffraction study shows zwitter ionic keto-amine tautomer form of planar Schiff base 1 that exists as dimer formed by C13 ̶ H13A•••O1i [(i) -x+1, -y, -z+1] hydrogen bonds and distorted octahedral geometry around Ni+2 center in chelate 2 where overall crystal structure stability may be credited to weak C ̶ H•••π, π•••π stacking, van der Waals interactions, and C ̶ H•••O type intermolecular hydrogen bonds. The anticancer activity has been investigated using cytotoxicity measure (MTT assay), apoptosis assay, quantitative polymerase chain reaction (qPCR), and colony formation assays. The Ni(II) metal complex demonstrates dose-dependent cytotoxicity in vitro, killing A549 lung cancer cells via an apoptotic pathway. MTT assay results direct to the fact that at higher concentration, 2 showed toxic effect in Beas-2B cells, while 1 showed almost similar cytotoxic effect (IC50=85.72 μM) as compared to A549 cells. On the A549 lung cancer cell line, the novel Ni(II) complex 2 has a good cytotoxic effect and causes apoptotic cell death. Colony forming assay study reveals that both 1 and 2 affect the proliferation and growth rate of cells at different doses, in fact, 2 inhibited colonization in HUH7 and HCT116 cells more than 1.
