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

In this study, a thioxanthone derivative, 2-Thioxanthone Thioacetic Acid (TXSCHCOOH) 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 TXSCHCOOH to ct-DNA. The intrinsic binding constant Kb of TXSCHCOOH-ct-DNA was found as 2.5 × 10 M from the absorption studies. Increasing of fluorescence emission intensity was found approximately 74.4% by adding ct-DNA to the TXSCHCOOH solution. Fluorescence microscopy was employed to display imaging of the TXSCHCOOH-ct-DNA solution. Increasing of the iodide quenching effect was observed when TXSCHCOOH was added to the double stranded DNA and the calculated quenching constants of TXSCHCOOH and TXSCHCOOH-ct-DNA were found to be 1.89 × 10 M and 1.19 × 10 M, 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 TXSCHCOOH demonstrated that the binding of TXSCHCOOH to ct-DNA was most likely groove binding. Furthermore, TXSCHCOOH 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. TXSCHCOOH exhibited notable cytotoxic activities compared to the standard chemotherapy drugs, fluorouracil (5-FU), cisplatin in tumorigenic HT29 cell line. The 50% growth-inhibitory concentration (IC) for TXSCHCOOH 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 TXSCHCOOH is activated by light indicates the potential of being theranostic cancer drug candidate.