A New Look into the Mode of Action of Metal-Based Anticancer Drugs

• Autor(a) principal: Marques, Maria P. M.
• Data de Publicação: 2020
• Outros Autores: Batista de Carvalho, Ana L. M., Mamede, A. P., Dopplapudi, Asha, Rudić, Svemir, Tyagi, Madhusudan, Garcia Sakai, Victoria, Batista de Carvalho, Luís A. E.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/106471; https://doi.org/10.3390/molecules25020246
• topic: palladium anticancer drug; DNA; hydration water; neutron scattering techniques; Raman; FTIR; Antineoplastic Agents; Cisplatin; DNA; Elasticity; Metals; Neutron Diffraction; Neutrons; Nucleic Acid Conformation; Palladium; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Spermine; Water

The mode of action of Pt- and Pd-based anticancer agents (cisplatin and Pd2Spm) was studied by characterising their impact on DNA. Changes in conformation and mobility at the molecular level in hydrated DNA were analysed by quasi-elastic and inelastic neutron scattering techniques (QENS and INS), coupled to Fourier transform infrared (FTIR) and microRaman spectroscopies. Although INS, FTIR and Raman revealed drug-triggered changes in the phosphate groups and the double helix base pairing, QENS allowed access to the nanosecond motions of the biomolecule's backbone and confined hydration water within the minor groove. Distinct effects were observed for cisplatin and Pd2Spm, the former having a predominant effect on DNA´s spine of hydration, whereas the latter had a higher influence on the backbone dynamics. This is an innovative way of tackling a drug´s mode of action, mediated by the hydration waters within its pharmacological target (DNA).