Antineoplastik İlaçların DNA ile Etkileşmelerinin UV-Görünür Bölge Spektroskopisi ile İncelenmesi

Abstract

Atmaca, L., Investigation of Interactions of Antineoplastic Drugs with DNA by UV-Visible Region Spectroscopy, Hacettepe University Graduate School of Health Sciences Department of Analytical Chemistry Master’s Thesis, Ankara, 2020. The primary goal in the treatment of cancer, which is caused by rapidly proliferating cells, is to suppress the uncontrolled proliferation of cells. Determining the type of interaction of DNA with some chemical substances (drugs, metals, environmental wastes, etc.) using different methods is important for the development of new drug designs. Many cancer drugs interact with DNA molecules. In this thesis; studies were performed to investigate the interactions of DNA and Gemcitabine HCl (GMB), which is a pyrimidine nucleoside, antineoplastic effective synthetic substance and Irinotecan HCl (ITN), which is an antineoplastic effective semisynthetic derivative of Camptothecin alkaloid by UV spectrophotometric method and illuminate their DNA binding mechanisms. The studies were performed both in aqueous medium and two different pH (pH 7.4 and pH 4.7) buffer solutions. According to the results obtained; it has been observed that the interaction mechanism with DNA for GMB and ITN is groove binding and intercalation, respectively. For the DNA-GMB complex, the binding constant value in the pH 7.4 buffer solution was calculated as 1948 M-1, while the binding constant value in the pH 4.7 buffer solution was calculated as 956 M-1. For the DNA-ITN complex, the binding constant value of the complex in the pH 7.4 buffer solution was calculated as 12632 M-1, while that of the complex in the pH 4.7 buffer solution was calculated as 10825 M-1 according to the peak at 220 nm and the binding constant value of the complex in the pH 7.4 buffer solution was calculated as 6348 M-1, while that of the complex in the pH 4.7 buffer solution was calculated as 2798 M-1 according to the peak at 255 nm. In the light of these data, it is understood that the binding constant is higher in blood pH. It has been observed that UV spectrophotometric method can be used in analysis of DNA-drug interactions. Keywords: DNA-Antineoplastic drug interactions, Gemcitabine hydrochloride, Irinotecan hydrochloride, UV-VIS spectroscopy.