PhD Scientific Days

Poster Presentation: Pharmaceutical

P02: Multispectroscopic analysis of DNA-binding of the anticancer drug sunitinib (Sutent ®)

Előadó neve

Kiss, Eszter

Előadó munkahelye

Semmelweis University, Department of Pharmaceutical Chemistry

Előadó telefonszáma

+36305964275

Előadó e-mail címe

kiss.eszter@pharma.semmelweis-univ.hu

Az előadás címe

Multispectroscopic analysis of DNA-binding of the anticancer drug sunitinib (Sutent ®)

Szerző(k) neve és munkahelye

Eszter Kiss
Semmelweis University, Department of Pharmaceutical Chemistry

Szekció

Poster Presentation: Pharmaceutical

Data of the presenter

Doctoral School of Pharmaceutical Sciences
Program: Modern Trends in Pharmaceutical Scientific Research
Supervisor: Péter Horváth
e-mail: kiss.eszter@pharma.semmelweis-univ.hu

Text of the abstract

Sunitinib is an orally used multi-targeted tyrosine kinase inhibitor, which is currently approved by the FDA for the treatment of renal cell carcinoma (RCC), gastrointestinal stomal tumors in case of progression or imatinib intolerance (GIST) and pancreatic neuroendocrine tumors. As a drug for human use it had to go through a set of in vivo genotoxicity testing which showed that the molecule had no mutagenic effect, however in vitro, in our research it obviously proved to bind to DNA. Our aim was to prove that CD spectroscopy is a reliable tool for predicting DNA binding of drug molecules.
In our research we used different spectroscopic methods (circular dichroism, CD-melting, nuclear magnetic resonance, UV spectroscopy) to determine whether sunitinib binds to DNA and the type of binding. For our measurements we used the pUC18 plasmide DNA, which has a well-defined size and characteristics, and the sunitinib base which was dissolved in DMSO at a 5 mM concentration. In the CD, UV measurements a constant concentration of DNA was titrated with different amounts of the sunitinib base. We also performed CD-melting studies on the pure DNA and also at two different sunitinib concentrations. In the NMR spectroscopic measurements we used the saturation transfer difference NMR (STD-NMR) method to help us determine the mode of the binding of the ligand. Our results revealed that sunitinib has somewhat different binding method at different concentrations. Analysing the positive and negative bands of DNA as well as the induced CD signal of the complex, we came to the conclusion that at lower concentrations the drug has an intercalative binding mode, but after a certain drug - basepair ratio it binds as an associate and the binding mode supposedly changes from intercalative to minor groove binding.

Azonosító

P02

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1111

Authors (legacy)