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DNA binding of sunitinib: Spectroscopic evidence via circular dichroism and nuclear magnetic resonance.
Kiss, Eszter; Mirzahosseini, Arash; Hubert, Ágnes; Ambrus, Attila; Orfi, László; Horváth, Péter.
Afiliación
  • Kiss E; Department of Pharmaceutical Chemistry, Semmelweis University, 1092 Budapest, Hogyes Endre utca. 9, Hungary. Electronic address: kiss.eszter@pharma.semmelweis-univ.hu.
  • Mirzahosseini A; Department of Pharmaceutical Chemistry, Semmelweis University, 1092 Budapest, Hogyes Endre utca. 9, Hungary. Electronic address: mirzahosseini.arash@pharma.semmelweis-univ.hu.
  • Hubert Á; Department of Medical Biochemistry, MTA-SE Laboratory for Neurobiochemistry, Semmelweis University, 1094 Budapest, Tuzoltó utca 37-47, Hungary. Electronic address: hubert.agnes@med.semmelweis-univ.hu.
  • Ambrus A; Department of Medical Biochemistry, MTA-SE Laboratory for Neurobiochemistry, Semmelweis University, 1094 Budapest, Tuzoltó utca 37-47, Hungary. Electronic address: ambrus.attila@med.semmelweis-univ.hu.
  • Orfi L; Department of Pharmaceutical Chemistry, Semmelweis University, 1092 Budapest, Hogyes Endre utca. 9, Hungary. Electronic address: orfi.laszlo@pharma.semmelweis-univ.hu.
  • Horváth P; Department of Pharmaceutical Chemistry, Semmelweis University, 1092 Budapest, Hogyes Endre utca. 9, Hungary. Electronic address: horvath.peter@pharma.semmelweis-univ.hu.
J Pharm Biomed Anal ; 150: 355-361, 2018 Feb 20.
Article en En | MEDLINE | ID: mdl-29287262
Sunitinib is a non-selective tyrosine kinase inhibitor, but in its chemical structure there can be discovered certain features, which suggest the ability to bind to DNA. These elements are the planar aromatic system and the tertiary amine function, which is protonated at the pH of the organism. In this study, the binding of the drug sunitinib to DNA was investigated using circular dichroism (CD), 1H NMR and UV spectroscopies, along with CD melting. For these studies DNA was isolated from calf thymus (CT), salmon fish sperm (SS), and chicken erythrocyte (CE), however for our purposes an artificially constructed and highly purified plasmid DNA (pUC18) preparation proved to be the most suitable. DNA binding of the drug was confirmed by shifts in the characteristic CD bands of the DNA, the appearance of an induced CD (ICD) signal in the upper absorption region of sunitinib (300 nm-500 nm), and the evidence from CD melting studies and the NMR. Based on the CD and NMR measurements, it can be assumed that sunitinib has a multiple-step binding mechanism.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plásmidos / Pirroles / ADN / Dicroismo Circular / Espectroscopía de Protones por Resonancia Magnética / Indoles / Antineoplásicos Idioma: En Revista: J Pharm Biomed Anal Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plásmidos / Pirroles / ADN / Dicroismo Circular / Espectroscopía de Protones por Resonancia Magnética / Indoles / Antineoplásicos Idioma: En Revista: J Pharm Biomed Anal Año: 2018 Tipo del documento: Article Pais de publicación: Reino Unido