Monodentate Phosphine Modulation in Cyclometallated Platinum(II) Complexes for Antileishmanial, Antiviral, and Antitumor Applications
Year: 2025
Type: article
Abstract: Complexes are emerging as promising alternatives for the treatment of neglected parasitic and viral infections, which urgently require new therapeutic strategies due to limited effective drugs. In this study, a series of [Pt(II)(phpy)(PR 3 )Cl] complexes, where phpy is 2‐phenylpyridine, and PR 3 represents triphenylphosphine (PPh 3 ), 1,3,5‐triaza‐7‐phosphaadamantane (PTA), para‐benzoic acid‐diphenylphosphine (PPh 2 (Ph p ‐COOH), or tris(2‐carboxyethyl)phosphine (TCEP), are synthesized and systematically evaluated for their chemical properties and in vitro biological activities. Chemical reactivity, including ligand exchange with L‐histidine and N ‐acetylcysteine, hydrophilic/lipophilic balance, and interactions with bovine serum albumin (BSA) and DNA, was correlated with biological outcomes. The novel TCEP complex exhibited exceptional chloride stability and intrinsic fluorescence but lacked antiviral and antileishmanial activity. The PTA derivative showed selective antileishmanial activity, achieving a selectivity index (SI) of 10.8 and reducing the infectivity index by 40% at 12 µM. Also, PTA showed selective antitumor activity in ovarian cancer (SI 9.1). In contrast, the PPh 2 (Ph p ‐COOH) derivative demonstrated significant antiviral activity, inhibiting Mayaro virus and Zika virus replication by 94% and 78%, respectively, at 50 µM. These findings underscore the potential of coordination chemistry to fine‐tune biological activity and support the rational design of metal‐based therapeutics for neglected diseases.
Source: ChemMedChem
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,150
Funders: Multiple System Atrophy Coalition, Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Financiadora de Estudos e Projetos, Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Centro Nacional de Processamento de Alto Desempenho em São Paulo
Awards: G116629194, G1426168670, “COMPLEXOS METÁLICOS COMO ABORDAGEM INOVADORA NO DESENVOLVIMENTO DE FÁRMACOS CONTRA VÍRUS EMERGENTES”, G2624804452, G2753085907, G2823776494, G29316538, G2995033815, G3690646728, G4506222160, G4592347666, G6191138830, G6815844370, COMPLEXOS METÁLICOS COMO ABORDAGEM INOVADORA NO DESENVOLVIMENTO DE FÁRMACOS CONTRA VÍRUS EMERGENTES, Evaluation of the biological profile of coordination complexes: an approach in 2D and 3D cell models, Design of novel metallodrugs and innovative administration routes for Leishmaniasis treatment
OpenAlex ID: W7117246275