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A New Look into the Mode of Action of Metal-Based Anticancer Drugs.
Marques, M Paula M; Batista de Carvalho, Ana L M; Mamede, Adriana P; Dopplapudi, Asha; Rudic, Svemir; Tyagi, Madhusudan; Garcia Sakai, Victoria; Batista de Carvalho, Luís A E.
Afiliação
  • Marques MPM; Unidade de I&D Química-Física Molecular, Department of Chemistry, University of Coimbra, Coimbra 3004-535, Portugal.
  • Batista de Carvalho ALM; Department of Life Sciences, University of Coimbra, Coimbra 3000-456, Portugal.
  • Mamede AP; Unidade de I&D Química-Física Molecular, Department of Chemistry, University of Coimbra, Coimbra 3004-535, Portugal.
  • Dopplapudi A; Unidade de I&D Química-Física Molecular, Department of Chemistry, University of Coimbra, Coimbra 3004-535, Portugal.
  • Rudic S; ISIS Facility, STFC Rutherford Appleton Laboratory, Chilton, Didcot OX11 0QX, UK.
  • Tyagi M; ISIS Facility, STFC Rutherford Appleton Laboratory, Chilton, Didcot OX11 0QX, UK.
  • Garcia Sakai V; NIST Center for Neutron Research, Gaithersburg, Maryland, MD 20899, USA.
  • Batista de Carvalho LAE; Department of Materials Science and Engineering, University of Maryland, College Park, Maryland MD 20742, USA.
Molecules ; 25(2)2020 Jan 07.
Article em En | MEDLINE | ID: mdl-31936161
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).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Cisplatino / Antineoplásicos Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Portugal

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA / Cisplatino / Antineoplásicos Idioma: En Revista: Molecules Assunto da revista: BIOLOGIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Portugal