Cu(II) complexes of hydrazones–NSAID conjugates: synthesis, characterization and anticancer activity

Abstract

The hydrazones of nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac and ibuprofen are synthesized with aldehydes of pyridine and imidazole and are characterized by ¹H, ¹³C and mass spectroscopy. Cu(II) complexes of hydrazones constructed from these ligands possess square planar geometry for bidentate diclofenac-hydrazone and tridentate ibuprofen-hydrazone conjugates with [Cu(L)₂] and [Cu(L)Cl] compositions, respectively. The observed irreversible Cu(II)/Cu(I) redox couple in the range of +0.20 to +0.61 V is due to the substantial distortion in the square-planar geometry. ESR studies indicate the appreciably covalent character within M–L bonding due to extensive delocalization of electron from d_x²_–-y² orbital. The hydrazone–NSAID conjugates exhibit substantial cytotoxicity against A-549, HCT-116 and MDA-MB-231 cancer cell lines with ibuprofen-imidazole-hydrazone ligand possessing the lowest IC₅₀ (2.26 µM) amongst the synthesized NSAID-conjugates. Interestingly, its Cu(II) complex also displays excellent anticancer activity against MDA-MB- 231 with IC₅₀ value of 3.58 µM. Such a feature may be ascribed to the synergistic association of Cu(II)–NSAID–hydrazone linkage. Thus, conjugation of NSAID with hydrazone and its complexation with a bioactive metal ion may be regarded as a potential strategy for designing of non-platinum anticancer agents.

Graphical Abstract

Keywords:

• Cu(II) complexes
• aroyl hydrazones
• NSAID
• anticancer activity
• ESR
• cyclic voltammetry

Disclosure statement

No potential conflict of interest was reported by the authors.

Acknowledgements

The authors are thankful to Principal, Abasaheb Garware College for the kind support. The authors express deep sense of gratitude to Dr. Shyamal Chattopadhyay, BESU, Kolkata, for analytical measurements.