Synthesis, spectral, Hirshfeld surface analysis and biological evaluation of a Schiff base copper(II) complex: Towards a copper(II) based human anti-glioblastoma agent

Abstract

Schiff base ligand 4-{(Z)-[(2-hydroxynaphthalen-1-yl)methylidene]amino}-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (HNMDP) was synthesized from 2-hydroxynaphthaldehyde and 4-aminoantipyrine. Since the ligand bears the suitable donor sites HCN (azomethine), hydroxyl and lactone carbonyl moieties it was reacted with Cu2+ to yield respective metal complex. The products were investigated by elemental analyses and IR spectroscopic techniques. Cu-NMDP crystallizes in the Ibam space group and forms a peculiar coordination polymer based on disordered acetate groups acting as bridging ligands producing distorted square planar geometry around copper. The molecular structure confirms the anticipated sites of coordination to be all involved in metal ion binding. The short interatomic interactions in the crystal structures were evaluated by mapping the Hirshfeld surface process using pseudo-mirrored 2D fingerprint plots. The major short interatomic interactions H···H, O···H and C···H cover the Hirshfeld surfaces. The interaction of the Schiff base ligand and its copper complex with human glioblastoma (malignant aggressive brain cancer) cells A172 and LN229 was studied. The copper complex on its own was found to be more active than its parent ligand. The Cu-NMDP IC50 values 5.698 µM after 72 h for A172 and 13.38 µM after 72 h for LN229 compared to HNMDP imply the copper based metallodrug to be a candidate for the chemotherapy of glioblastoma.