Novel Bidentate Amine Ligand and the Interplay between Pd(II) and Pt(II) Coordination and Biological Activity

Abstract

Pt(II) and Pd(II)‐coordinating N‐donor ligands have been extensively studied following the success of cisplatin. In this work, a novel bidentate N‐donor ligand, the N‐[[4‐(phenylmethoxy)phenyl]methyl]‐2‐pyridinemethanamine ligand, was designed to explore the antiparasitic, antiviral, and antitumor activity of its Pt(II) and Pd(II) complexes. The ligand incorporates a benzyloxybenzyl moiety reported to improve the biological activity of several organic drugs. Chemical and spectroscopic characterization confirms the formation of [M(L)Cl2] complexes, where M = Pt(II) and Pd(II). Single crystal X‐ray diffraction confirmed a square‐planar geometry for the Pd(II) complex, and spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1H‐NMR, 195Pt‐NMR, and HR‐MS analysis of DMSO solutions of the complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for in vitro antitumoral, antileishmanial, and antiviral activities. The Pt(II) complex resulted in a GI50 value of 10.5 μM against the NCI‐ADR/Res (multidrug‐resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti‐SARS‐CoV‐2 activity, with around a 65% reduction in viral replication at a concentration of 50 μM.