The interaction of light-activatable 2-thioxanthone thioacetic acid with ct-DNA and its cytotoxic activity: Novel theranostic agent

被引：8
作者：
Ataci N. [1 ]
Kazancioglu E.O. [1 ]
Kalındemirtas F.D. [2 ]
Kuruca S.E. [2 ]
Arsu N. [1 ]
机构：
[1] Yildiz Technical University, Department of Chemistry, Davutpasa Campus, Istanbul
[2] Istanbul University, Faculty of Medicine, Department of Physiology, Istanbul
来源：
Arsu, Nergis (narsu@yildiz.edu.tr) | 1600年 / Elsevier B.V., Netherlands卷 / 239期
关键词：
Binding mode; Calf thymus DNA; Cell cytotoxicity; Fluorescence titration; Groove binding; Spectroscopy; Thioxanthone derivative;
D O I：
10.1016/j.saa.2020.118491
中图分类号：
学科分类号：
摘要：
In this study, a thioxanthone derivative, 2-Thioxanthone Thioacetic Acid (TXSCH2COOH) was used to analyze the type of binding to calf thymus DNA in a physiological buffer (Tris-HCl buffer solution, pH:7.0). Several spectroscopic techniques were employed including UV–Vis absorption and fluorescence emission spectroscopy and viscosity measurements were also used to clarify the binding mode of TXSCH2COOH to ct-DNA. The intrinsic binding constant Kb of TXSCH2COOH-ct-DNA was found as 2.5 × 103 M−1 from the absorption studies. Increasing of fluorescence emission intensity was found approximately 74.4% by adding ct-DNA to the TXSCH2COOH solution. Fluorescence microscopy was employed to display imaging of the TXSCH2COOH-ct-DNA solution. Increasing of the iodide quenching effect was observed when TXSCH2COOH was added to the double stranded DNA and the calculated quenching constants of TXSCH2COOH and TXSCH2COOH-ct-DNA were found to be 1.89 × 103 M−1 and 1.19 × 104 M−1, respectively. Additionally, the iodide quenching experiment was conducted with single stranded DNA which led to a high Ksv value. All the experimental results including the viscosity values of ct-DNA with TXSCH2COOH demonstrated that the binding of TXSCH2COOH to ct-DNA was most likely groove binding. Furthermore, TXSCH2COOH was found to be an A-T rich minor groove binder. This was confirmed by the displacement assays with Hoechst 33258 compared to Ethidium Bromide. The in vitro cytotoxic activity measurements were performed by MTT assay on HT29 cell line for 72 h. TXSCH2COOH exhibited notable cytotoxic activities compared to the standard chemotherapy drugs, fluorouracil (5-FU), cisplatin in tumorigenic HT29 cell line. The 50% growth-inhibitory concentration (IC50) for TXSCH2COOH was 19,8 μg/mL while 5-FU and cisplatin were 28.9 μg/mL, 20 μg/mL, respectively. The increase in cytotoxic effect when TXSCH2COOH is activated by light indicates the potential of being theranostic cancer drug candidate. © 2018 Elsevier B.V.
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