Agradecimentos: Authors thanks the Karen C. Minori support on cell studies (FAPESP #2023/06493-0). L. S. O. thanks to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Brazil for the PhD fellowship (#99997479777/2020-00). I. A. S. thanks to National Council for Scientific and Technological Development (CNPq), for scholarship #142495/2020-4, and CAPES.PrInt-UFU sandwich scholarship #88887.700246/2022-00. J. C. S. thanks to CAPES for the master fellowship (#88887.712507/2022-00). Work in the M. H. laboratory was supported by a Wellcome Investigator Award (#096670) and an MRC project grant (MR/S001026/1). The purchase of the Incucyte S3 system was funded by a Wellcome multi-user equipment grant (#221538/Z/20/Z). A. C. G. J. is grateful to FAPEMIG (Minas Gerais Research Foundation APQ-01487-22 and APQ-04686-22) and to CAPES (Prevention and Combat of Outbreaks, Endemics, Epidemics and Pandemics–Finance Code #88881.506794/2020-01 and –Finance Code 001). A. L. T. G. R. was supported by CNPq (#313440/2019-0, and #429463/2018-9) and the Fund for Support to Teaching, Research and Outreach Activities of the University of Campinas (FAEPEX/Unicamp, grants #2001/19, #2555/20, and #2235/21). D. C. M. and C. A. are Research Productivity Fellows from CNPq. D. C. M. laboratory was supported by Pró-Reitoria de Pesquisa – UNICAMP (#519.292 – FAEPEX/PRP/FAEPEX-Pesquisa). C. A. was supported by FAPESP (#2019/16904-2 and #2022/02618-0) and CNPq (#406444/2018-8 and #404668/2021-6) Ver menos

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 Ver menos