Novel bidentate amine ligand and the interplay between Pd(II) and Pt(II) coordination and biological activity

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Oliveira, Laiane S. ; Rosa, Leticia B. ; Affonso, Daniele D. ; Santos, Igor A. ; Da Silva, Jennyfer C. ; Rodrigues, Gustavo C. ; Harris, Mark ; Jardim, Ana Carolina G. ; Nakahata, Douglas H. ; Sabino, Jose R. ; de Carvalho, Joao E. ; Miguel, Danilo C. ; Ruiz, Ana Lucia T. G. ; Abbehausen, Camilla

• Document type: Journal article
• Source: CHEMBIOCHEM; v. 25, n. 6, p. 11-pg., 2024-02-12.

Abstract

Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl2] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1H NMR, 195Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of 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 activity. The Pt(II) complex resulted in a GI50 of 10.5 mu M 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 65 % reduction in viral replication at a concentration of 50 mu M. The novel N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine (L) coordinates Pt(II) and Pd(II) giving two complexes of formula [MLCl2]. The ligand and Pd(II) complex impaired 65 % and 59 %, respectively, of SARS-CoV-2 replication at the viable concentrations of 50 mu M. In the in vitro antitumor evaluation, Pt(II) complex showed significant cytotoxicity with a GI50 of 10 mu M, and no selectivity in the panel of tumor cells evaluated. image (AU)

• FAPESP's process: 22/02618-0 - Design of novel metallodrugs and innovative administration routes for Leishmaniasis treatment
• Grantee: Camilla Abbehausen
• Support Opportunities: Research Grants - Initial Project
• FAPESP's process: 19/16904-2 - Targeted metallodrug design for antileishmaniasis
• Grantee: Camilla Abbehausen
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/06493-0 - Cell culture routine implementation
• Grantee: Karen Caroline Minori Vieira
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training