Anticancer activities and cell death mechanisms of 1H-indole-2,3-dione 3-[N-(4 sulfamoylphenyl)thiosemicarbazone] derivatives

Year 2018, Volume 48, Issue 3, 63 - 67, 01.12.2018

İdil ÇETİN Pınar ERASLAN ELMA Mehmet TOPÇUL Nilgün KARALI

Abstract

DOI: 10.26650/IstanbulJPharm.2018.414805

In this study, the cytotoxic effects of 1H-indole-2,3-dione 3-[N-(4-sulfamoylphenyl)thiosemicarbazone derivatives namely, 4a-d were evaluated using cell kinetic parameters including the cell index, mitotic index, labelling index and apoptotic index on HeLa cells taken from a human cervix carcinoma. All compounds were evaluated using cell index parameters at 5, 10, 20, 40, 80, 100 and 160 μM concentrations. As a result of this, it was seen that all 4a-d compounds were effective in different concentrations. Different cell death mechanisms were proposed for 4a-d. When all the parameters were examined, it was found that the bromine substituted 4c was the most potent antiproliferative compound in the tested compounds. The difference was significant between the control and experimental groups (p<0.01). In addition, a statistically significant difference was noted among all experimental groups (p<0.01).

Keywords

1H-indole-2, 3-dione, thiosemicarbazone, antiproliferative effect, HeLa cells

References

• • Cetin I, Topcul MR (2017). In vitro antiproliferative effects of nab-paclitaxel with liposomal cisplatin on MDA-MB-231 and MCF-7 breast cancer cell lines. J BUON 22: 347-354.
• • Eldehna WM, Altoukhy A, Mahrous H, Abdel-Aziz HA (2015). Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents. Eur J Med Chem 90: 684-694.
• • Gabr MT, El-Gohary NS, El-Bendary ER, El-Kerdawy MM, Ni N (2017). Isatin-β-thiocarbohydrazones: Microwave-assisted synthesis, antitumor activity and structure-activity relationship. Eur J Med Chem 128: 36-44.
• • Hall MD, Salam NK, Hellawell JL, Fales HM, Kensler CB, Ludwig JA, Szakács G, Hibbs DE, Gottesman MM (2009). Synthesis, activity, and pharmacophore development for isatin-β-thiosemicarbazones with selective activity toward multidrug-resistant cells. J Med Chem 52: 3191-3204.
• • Karalı N, Gürsoy A, Kandemirli F, Shvets N, Kaynak FB, Özbey S, Kovalishyn V, Dimoglo A (2007). Synthesis and structure antituberculosis activity relationship of 1H-indole-2,3-dione derivatives. Bioorg Med Chem 15: 5888-5904.
• • Karalı N, Akdemir A, Göktaş F, Eraslan Elma P, Angeli A, Kızılırmak M, Supuran CT (2017). Novel sulfonamide-containing 2-indolinones that selectively inhibit tumor-associated alpha carbonic anhydrazes, Bioorg Med Chem 25: 3714-3718.
• • Liu W, Zhu HM, Niu GJ, Shi, EZ, Chen J, Sun B, Chen WQ, Zhou HG, Yang C (2014). Synthesis, modification and docking studies of 5-sulfonylisatin derivatives as SARS-CoV 3C-like protease inhibitors. Bioorg Med Chem 22: 292-302.
• • Lv K, Wang LL, Liu ML, Zhou XB, Fan SY, Liu HY, Zheng ZB, Li S (2011). Synthesis and antitumor activity of 5-[1-(3-(dimethylamino)propyl)-5-halogenated-2-oxoindolin-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxamides. Bioorg Med Chem Lett 21: 3062-3065.
• • Pakravan P, Kashanian S, Khodaei MM, Harding FJ (2013). Biochemical and pharmacological characterization of isatin and its derivatives: from structure to activity. Pharmacol Rep 65: 313-335.
• • Pape VFS, Tóth S, Füredi A, Szebényi K, Lovrics A, Szabó P, Wiese M, Szakács G (2016). Design, synthesis and biological evaluation of thiosemicarbazones, hydrazinobenzothiazoles and arylhydrazones as anticancer agents with a potential to overcome multidrug resistance. Eur J Med Chem, 117: 335-354.
• • Patel A, Bari S, Talele G, Patel J, Sarangapani M (2006). Synthesis and antimicrobial activity of some new isatin derivatives. Iran J Pharm Res 4: 249-254.
• • Remesh A (2012). Toxicities of anticancer drugs and its management. Int J Basic Clin Pharmacol 1: 2-12.
• • Sarkar FH, Li Y (2006). Using chemopreventive agents to enhance the efficacy of cancer therapy. Cancer Res 66: 3347-3350.
• • Singh A, Raghuwanshi K, Patel VK, Jain DK, Veerasamy R, Dixit A, Rajak H (2017). Assessment of 5-substituted isatin as surface recognition group: Design, synthesis, and antiproliferative evaluation of hydroxamates as novel histone deacetylase inhibitors. Pharm. Chem. J 51: 366-374.
• • Topcul MR, Cetin I, Kolusayın Ozar MO (2013). The effects of anastrozole on the proliferation of Fm3a cells. J BUON 18: 874-878.
• • Vine KL, Matesic L, Locke JM, Ranson M, Skropeta D (2009). Cytotoxic and Anticancer Activities of Isatin and Its Derivatives: A Comprehensive Review from 2000-2008. Anticancer Agents Med Chem 9: 397-414.
• • World Health Organization, http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed February 2018.
• • Zhou L, Liu Y, Zhang W, Wei P, Huang C, Pei J, Yuan Y, Lai L (2006). Isatin compounds as noncovalent SARS coronavirus 3C-like protease inhibitors. J Med Chem 49: 3440-3443.