Research Article

Synthesis of New Anthraquinone Derivatives and Anticancer Effects on Breast Cancer Cell Lines

Number: 4 December 4, 2018
  • Ebru Hacıosmanoglu
  • Funda Ozkok
  • Alper Kemal Onsu
  • Muhammet Bektas
  • Basak Varol
  • Sacide Pehlıvan
EN

Synthesis of New Anthraquinone Derivatives and Anticancer Effects on Breast Cancer Cell Lines

Abstract

Antraquinone and their analogues are among the important compounds investigated to develop novel bioactive and biocompatible molecules with potential for medical applications. The most important quinone class as anthraquinones occur widely in plants such as aloe vera and tipton's weed. Anthraquinone derivatives have aroused special interest since they have demonstrated potential therapeutic uses as antibacterial, antiviral, antifungal agents and other biological activities. Mitoxantrone, an anthraquinone analogue, is known as a synthetic anticancer analog of anthracycline antibiotics. Mitoxantrone as anticancer drug is a powerful inhibitor of the enzyme that is in charge with the repair of damaged DNA. In this study, new anthraquinone derivatives([1-(4-Chlorothiophenyl)-9,10-dioxoanthraquinone],[1-(4-Aminothiophenyl)-9,10 dioxoanthraquinone]) were characterized by spectroscopic methods (1H-NMR, 13C-NMR, FT-IR, UV-Vis analyzes). Breast cancer cell lines (MDA- MB-231 and MCF-7) and human umbilical vein endothelial cells (HUVECs) were proliferated in standard culture conditions. Cells were incubated with these derivatives for 24 and 48 h with in different concentrations. Cell proliferation assays, MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and CCK-8 (Cell Counting Kit-8), were performed to reveal anticancer effect of new anthraquinone derivatives. As a result, Cell viability of MDA- MB-231 and MCF-7 cells were decreased significantly (p<0.05) by new anthraquinone derivatives treatment whereas cytotoxic effect was not observed in HUVECs. In this study new synthesized anthraquinone derivatives were tested and comparable results were observed both in vitro cytotoxicity assay and statistical analysis. This anthraquinone derivatives are promising for its further development as an anticancer drug.

Keywords

References

  1. Almutairi, M. S., Hegazy, G. H., Haiba, M. E., Ali, H. I., Khalifa, N. M., & Soliman Ael, M. (2014). Synthesis, docking and biological activities of novel hybrids celecoxib and anthraquinone analogs as potent cytotoxic agents. Int J Mol Sci, 15(12), 22580-22603. doi:10.3390/ijms151222580 Errington, R. J., Sadiq, M., Cosentino, L., Wiltshire, M., Sadiq, O., Sini, M., . . . Pors, K. (2018). Probing cytochrome P450 bioactivation and fluorescent properties with morpholinyl-tethered anthraquinones. Bioorg Med Chem Lett, 28(8), 1274-1277. doi:10.1016/j.bmcl.2018.03.040 Ferrazzi, E., Palumbo, M., Valisena, S., Antonello, C., & Palu, G. (1986). Antitumor activity of new anthraquinone derivatives. Chemioterapia, 5(5), 330-336. Huang, H. S., Chiou, J. F., Chiu, H. F., Hwang, J. M., Lin, P. Y., Tao, C. W., . . . Jeng, W. R. (2002). Synthesis of symmetrical 1,5-bis-thio-substituted anthraquinones for cytotoxicity in cultured tumor cells and lipid peroxidation. Chem Pharm Bull (Tokyo), 50(11), 1491-1494. Iqbal, J., Saeed, A., Raza, R., Matin, A., Hameed, A., Furtmann, N., . . . Bajorath, J. (2013). Identification of sulfonic acids as efficient ecto-5′-nucleotidase inhibitors. European Journal of Medicinal Chemistry, 70, 685-691. doi:https://doi.org/10.1016/j.ejmech.2013.10.053 Locatelli, M., Epifano, F., Genovese, S., Carlucci, G., Koncic, M. Z., Kosalec, I., & Kremer, D. (2011). Anthraquinone profile, antioxidant and antimicrobial properties of bark extracts of Rhamnus catharticus and R. orbiculatus. Nat Prod Commun, 6(9), 1275-1280. Meran, M., Akkus, P. D., Kurkcuoglu, O., Baysak, E., Hizal, G., Haciosmanoglu, E., . . . Guner, F. S. (2018). Noncovalent Pyrene-Polyethylene Glycol Coatings of Carbon Nanotubes Achieve in Vitro Biocompatibility. Langmuir, 34(40), 12071-12082. doi:10.1021/acs.langmuir.8b00971 Nobili, S., Lippi, D., Witort, E., Donnini, M., Bausi, L., Mini, E., & Capaccioli, S. (2009). Natural compounds for cancer treatment and prevention. Pharmacol Res, 59(6), 365-378. doi:10.1016/j.phrs.2009.01.017 Ozkok, F and Şahin, YM. (2016). Biyoaktif Antrakinon Anologlarının Sentezine Yönelik Özgün Metot Geliştirilmesi, TÜRKIYE, Patent, TR 2016/19610 Palumbo, M., Palu, G., Gia, O., Ferrazzi, E., Gastaldi, S., Antonello, C., & Meloni, G. A. (1987). Bis-substituted hydroxy-anthracenediones: DNA binding and biological activity. Anticancer Drug Des, 1(4), 337-346. Pickhardt, M., Gazova, Z., von Bergen, M., Khlistunova, I., Wang, Y., Hascher, A., . . . Mandelkow, E. (2005). Anthraquinones inhibit tau aggregation and dissolve Alzheimer's paired helical filaments in vitro and in cells. J Biol Chem, 280(5), 3628-3635. doi:10.1074/jbc.M410984200 Rassu, M., Ferrazzi, E., Stefanelli, S., Palu, G., Antonello, C., & Palumbo, M. (1991). [Structure-activity relationship of several mitoxantrone analogues]. G Ital Chemioter, 38(1-3), 201-203. Wang, W., Bai, Z., Zhang, F., Wang, C., Yuan, Y., & Shao, J. (2012). Synthesis and biological activity evaluation of emodin quaternary ammonium salt derivatives as potential anticancer agents. Eur J Med Chem, 56, 320-331. doi:10.1016/j.ejmech.2012.07.051

Details

Primary Language

English

Subjects

-

Journal Section

Research Article

Authors

Ebru Hacıosmanoglu This is me

Funda Ozkok This is me

Alper Kemal Onsu This is me

Muhammet Bektas This is me

Basak Varol This is me

Sacide Pehlıvan This is me

Publication Date

December 4, 2018

Submission Date

November 21, 2018

Acceptance Date

-

Published in Issue

Year 2018 Number: 4

APA
Hacıosmanoglu, E., Ozkok, F., Onsu, A. K., Bektas, M., Varol, B., & Pehlıvan, S. (2018). Synthesis of New Anthraquinone Derivatives and Anticancer Effects on Breast Cancer Cell Lines. The Eurasia Proceedings of Science Technology Engineering and Mathematics, 4, 271-276. https://izlik.org/JA28MJ42XL