Cytotoxic palladium(II) complexes of 8-aminoquinoline derivatives and the interaction with human serum albumin

Palladium(II) complexes are potential antitumor metallodrugs for their chemical resemblance to platinum(II) complexes. Two palladium(II) complexes (1 and 2) in the formula of [PdLnCl] [L1 = N-(tert-butoxycarbonyl)-l-methionine-N′-8-quinolylamide, L2 = L-alanine-N′-8-quinolylamide] have been synthesized accordingly. The structures of the complexes were fully characterized by X-ray crystallography. The palladium(II) center in 1 is coordinated by two N atoms and an S atom from L1 with one chloride anion as the leaving group; while that in 2 is coordinated by three N atoms from L2 with one chloride anion as the leaving group. The interaction between complex 1 and human serum albumin (HSA) has been investigated using fluorescence and circular dichroism spectroscopies. The complex seems to react with HSA chiefly through hydrophobic and electrostatic interactions, and it does not alter the α-helical nature of HSA. The cytotoxicity of these complexes has been tested against the human cervical cancer (HeLa), human mammary cancer (MCF-7), and human lung cancer (A-549) cell lines. Complex 1 displays a cytotoxic activity comparable to that of cisplatin, but complex 2 is less active than cisplatin.

Graphical abstractPalladium(II) complexes of ligands with steric hindrance could be equally cytotoxic toward tumor cells but less active to human serum albumin in comparison with cisplatin.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Pd(II) complexes of quinoline derivatives with monofunctional structural features ► Pd(II) complexes binds to serum albumin through non-covalent interactions ► Pd(II) complexes demonstrate comparable cytotoxicity to cisplatin