Publications by authors named "Ferdane Danışman-Kalındemirtaş"

3 Publications

  • Page 1 of 1

Selective Cytotoxic Effects of 5-Trifluoromethoxy-1H-indole-2,3-dione 3-Thiosemicarbazone Derivatives on Lymphoid-originated Cells.

Anticancer Agents Med Chem 2021 Mar 1. Epub 2021 Mar 1.

Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34116 Beyazıt, Istanbul. Turkey.

Aim: The present study aims to identify the anticancer effect of novel 1H-indole-2,3-dione 3-thiosemicarbazone derivatives. These compounds could be promissing anticancer agents in leukemia treatment.

Background: Conventional chemotherapeutic agents accumulate in both normal and tumor cells due to non-specificity. For effective cancer treatment, new drugs need to be developed to make chemotherapeutics selective for cancer cells. The ultimate goal of cancer treatment is to reduce systemic toxicity and improve the quality of life.

Method: In this study, the anticancer effects of 5-trifluoromethoxy-1H-indole-2,3-dione 3-thiosemicarbazone derivatives (A-L) were investigated in chronic myelogenous leukemia K562, Burkitt's lymphoma P3HR1, acute promyelocytic leukemia HL60 cells and vincristine-resistant sublines of K562 and P3HR1 cells. Additionally, the compounds were tested on lymphoid derived cells from ALL patients. In order to investigate the particular mechanism of death caused by the cytotoxic effects of the compounds, immunohistochemical caspase 3 staining was performed in P3HR1 cells, and resulting apoptotic activities were demonstrated.

Result: All compounds tested have been found to have cytotoxic effects against lymphoma cells at submicromolar concentrations (IC50= 0.89-1.80 µM). Most compounds show significant selectivity for the P3HR1 and P3HR1 Vin resistant. The most effective and selective compound is 4-bromophenyl substituted compound I (IC50=0.96 and 0.89 µM). Cyclohexyl and benzyl substituted compounds D and E have also been found to have cytotoxic effects against K562 cell lines (IC50=2.38 µM), while the allyl substituted compound C is effective on all cell lines (IC50=1.13-2.21 µM). 4-Fluorophenyl substituted F compound has been observed to be effective on all cells (IC50=1.00-2.41 µM) except K562 cell. Compound C is the only compound that shows inhibition of HL-60 cells (IC50= 1.13 µM). Additionally, all compounds exhibited cytotoxic effects on lymphoid-derived cells at 1µM concentration. These results are in accordance with the results obtained in lymphoma cells.

Conclusion: All compounds tested have submicromolar concentrations of cytotoxic effects on cells. These compounds hold promise for the future treatment of leukemia cancer.
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http://dx.doi.org/10.2174/1871520621666210302084230DOI Listing
March 2021

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

Spectrochim Acta A Mol Biomol Spectrosc 2020 Oct 16;239:118491. Epub 2020 May 16.

Yildiz Technical University, Davutpasa Campus, Department of Chemistry, 34220 Istanbul, Turkey. Electronic address:

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.
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http://dx.doi.org/10.1016/j.saa.2020.118491DOI Listing
October 2020

Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

Balkan Med J 2019 02 5;36(2):96-105. Epub 2018 Nov 5.

Department of Physiology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey

Background: Flavonoids are natural compounds with antioxidant, anticarcinogenic, and anti-inflammatory effects.

Aims: To determine the cytotoxic effects of flavonoids and drug resistance related to P-gp on K562 human chronic myeloid leukemia cells. We also aimed to evaluate the therapeutic potential of imatinib and flavonoid combinations.

Study Design: Cell culture study.

Methods: In this study, K562 cells were treated with apigenin, luteolin, 5-desmethyl sinensetin and the anticancer drug imatinib mesylate. The effect of flavonoids on K562 cell proliferation was detected using the 3-(4,5-dimethylthiazolyl)2,5‑diphenyl‑tetrazolium bromide assay. Concentrations of apigenin, luteolin, and 5-desmethyl sinensetin ranging from 25 to 200 μM and of imatinib from 5 to 50 μM administered for 72 h were studied. Apoptosis/necrosis and P-gp activity were measured using flow cytometry. The combined effects of different concentrations of flavonoids with imatinib were evaluated according to combination index values calculated using CompuSyn software.

Results: In our study, the IC values for apigenin, luteolin, and 5-desmethyl sinensetin were found to be 140 μM, 100 μM, and >200 μM, respectively. Luteolin (100 μM) had the highest cytotoxic activity of these flavonoids. These results were statistically significant (p<0.05). Among the flavonoids studied, the combination of luteolin and imatinib was the most effective and is therefore recommended for its cytotoxic activity in the K562 cell line. After 72 h of incubation at their respective IC concentrations, all flavonoids were associated with an apoptosis rate of approximately 50%. P-glycoprotein activity was increased in all groups. Combination treatment may provide better outcomes in terms of cytotoxicity and thus reduce the dosages of imatinib used.

Conclusion: The combination of some flavonoids and imatinib mesylate may increase the cytotoxic effect; However, the antagonistic effect should be considered in combined use on k562 cells.
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http://dx.doi.org/10.4274/balkanmedj.galenos.2018.2017.1244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409953PMC
February 2019