IN VITRO CYTOTOXICITY AND FREE RADICAL SCAVENGING POTENTIAL OF ETHYL PYRUVATE DERIVED COPPER COMPLEXES OF THIOSEMICARBAZONE

Authors

  • Kittur R. Asha Davangere University
  • Heggodu G. Rohitkumar Davangere University
  • Kalagouda B. Gudasi Karnatak Universit
  • Gopal M. Advi Rao Department of Biochemistry, Davangere University, Davangere 577002

Keywords:

Thiosemicarbazone, Cytotoxicity, Antioxidant, Leukemia, Anticancer drug

Abstract

Objective: The present study was aimed to evaluate the cytotoxicity and antioxidant properties of copper complexes of thiosemicarbazone (TSC-Cu) using different in vitro models.

Methods: In vitro MTT assay was carried out against the HL-60 cell line to check the cytotoxic potency of TSC-Cu. In vitro radical scavenging activity of TSC-Cu was evaluated by checking its role in scavenging DPPH, hydroxyl radical and lipid peroxidation.

Results: Among the test molecules studied, TSC-Cu with choride side chain (TSC-Cu-Cl) showed dose and time dependent increased cytotoxic activity on HL-60 cell line compared to TSC-Cu with hydroxyl side chain (TSC-Cu-OH). Further, TSC-Cu-Cl exhibited promising radical scavenging activities against hydroxyl radical, 2,2-diphenyl, 2-picryl hydrazyl (DPPH), and also effectively inhibited lipid peroxidation.

Conclusion: The results of the present investigation confirm that the TSC-Cu-Cl complex can be considered as a novel metal complex with potent anti-oxidant and cytotoxic ability.

 

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References

Perez VI, Bokov A, Remmen HV, Mele J, Ran Q, Ikeno Y, et al. Is the oxidative stress theory of aging dead? Biochim Biophys Acta 2009;1790:1005-14.

Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation and cancer: How are they linked? Free Radic Biol Med 2010;49:1603–16.

Lakshmi SV, Padmaja G, Kuppuswamy P, Kutala VK. Oxidative stress in cardiovascular disease. Indian J Biochem Biophys 2009;46:421-40.

Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes 1991;40:405-12.

Perry G, Cash AD, Smith MA. Alzheimer disease and oxidative stress. J Biomed Biotechnol 2002;2:120–3.

Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer 2003;3:276-86.

Cerutti PA, Trump BF. Inflammation and oxidative stress in carcinogenesis. Cancer Cells 1991;3:1-7.

Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, et al. Oxidative stress, prooxidants, and antioxidants: the interplay. BioMed Res Int 2014; doi.org/10.1155/2014/761264. [Article in Press]

Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010;4:118–26.

Yeo JD, Jeong MK, Park CU, Lee J. Comparing antioxidant effectiveness of natural and synthetic free radical scavengers in thermallyâ€oxidized lard using DPPH method. J Food Sci 2010;75:C258-62.

Crim JA, Petering HG. The antitumor activity of Cu(ii)KTS, the copper(II) chelate of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone). Cancer Res 1967;27:1278–85.

Subczynski WK, Antholine WE, Hyde JE. Dynamics of raft molecules in the cell and artificial membranes: approaches by pulse EPR spin labeling and single molecule optical microscopy. J Am Chem Soc 1987;109:46-52.

Kappus H. Overview of enzyme systems involved in bio-reduction of drugs and in redox cycling. Biochem Pharmacol 19861;35:1–6.

Gant TW, Rao DNR, Mason RP, Cohen GM. Redox cycling and sulphydryl arylation; their relative importance in the mechanism of quinone cytotoxicity to isolated hepatocytes. Chem Biol Interact 1988;65:157–73.

Miller III MC, Stineman CN, Vance JR, West DX, Hall IH. The cytotoxicity of copper(II) complexes of 2-acetyl-pyridyl-4N-substituted thiosemicarbazones. Anticancer Res 1998;18:4131–40.

Aishakhanam HP, Asha KR, Raghavendra PB, Ganesh NN, Rohit Kumar HG, Christopher SF, et al. Association of late transition metal complexes with ethyl 2-(2-(4-chlorophenylcarbamothioyl)hydrazono)propanoate: Design, synthesis and in vitro anticancer studies. Inorg Chim Acta 2015;430:216–24.

Mosmann TJ. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Immunol Methods 1983;65:55–63.

Chiruvella KK, Kari V, Choudhary B, Nambiar M, Ghanta RG, Raghavan SC. Methyl angolensate, a natural tetranortriterpenoid induces intrinsic apoptotic pathway in leukemic cells. FEBS Lett 2008;582:4066–76.

RohitKumar HG, Asha KR, Kiran Kumar HN, Inamdar LS, Advi Rao GM. Cell cycle arrest and induction of apoptosis in colon adenocarcinoma cells by a DNA intercalative quinoline derivative, 4-morpholinopyrimido [4',5':4,5] selenolo (2,3-b) quinoline. Nucleosides Nucleotides Nucleic Acids 2015;34:525-43.

Puneeth HR, Sharada AC. Antioxidant and hypoglycemic effects of curcumin pyrazole derivatives. Int J Pharm Pharm Sci 2015;7:244–9.

Halliwell B, Gutteridge JMC, Aruoma OI. The deoxyribose method: a simple ‘test tube’ assay for determination of rates constants for reactions of hydroxyl radical. Anal Biochem 1987;165:215-24.

Ohkawa H, Ohishi N, Yagi K. Assay of lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8.

Vara D, Pula G. Reactive oxygen species: physiological roles in the regulation of vascular cells. Curr Mol Med 2014;14:1103–25.

Liou GY, Storz P. Reactive oxygen species in cancer. Free Radic Res 2010;44:479–96.

Wang J, Yi J. Cancer cell killing via ROS: To increase or decrease, that is a question. Cancer Biol Ther 2010;7:1875–84.

Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin Interventions Aging 2007;2:219–36.

Wang D, Lippard SJ. Cellular processing of platinum anticancer drugs. Nat Rev Drug Discovery 2005;4:307–20.

El-Wakiel N, El-Keiy M, Gaber M. Synthesis, spectral, antitumor, antioxidant and antimicrobial studies on Cu(II), Ni(II) and Co(II) complexes of 4-[(1H Benzoimidazol-2-ylimino)-methyl]-benzene-1,3-diol. Spectrochim Acta Part A 2015;147:117–23.

Pereira RMS, Andrades NED, Paulino N, Sawaya ACHF, Eberlin MN, Marcucci MC, et al. Synthesis and characterization of a metal complex containing naringin and cu, and its antioxidant, antimicrobial, antiinflammatory and tumor cell cytotoxicity. Molecules 2007;12:1352–66.

Kavitha P, Reddy KL. Synthesis, structural characterization, and biological activity studies of Ni(II) and Zn(II) complexes. Bioinorg Chem Appl 2014; doi.org/10.1155/2014/568741. [Article in Press]

Anitha P, Chitrapriya N, Jang YJ, Viswanathamurthi P. Synthesis, characterization, DNA interaction, antioxidant and anticancer activity of new ruthenium(II) complexes of thiosemicarbazone/semicarbazone bearing 9,10-phenanthrenequinone. J Photochem Photobiol B 2013;129:17–26.

Gujarathi JR, Pawar NS, Bendre RS. Synthesis, spectral and antioxidant assay of Nickel (II) adducts with heterocyclic bases derived from 5-chloro-2-hydroxy acetophenone N methyl thiosemicarbazone. Pharm Chem 2013;5:120–5.

Pahontu E, Fala V, Gulea A, Poirier D, Tapcov V, Rosu T. Synthesis and characterization of some new Cu(II), Ni(II) and Zn(II) complexes with salicylidene thiosemicarbazones: antibacterial, antifungal and in vitro antileukemia activity. Molecules 2013;18:8812–36.

Ingo Ott. On the medicinal chemistry of gold complexes as anticancer drugs. Coord Chem Rev 2009;253:1670–81.

Smith FE. Tetrazolium Salt. Science 1951;113:751–4.

Shahabuddin MS, Nambiar M, Choudhary B, Advirao GM, Raghavan SC. A novel DNA intercalator, butylamino-pyrimido[4',5':4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells. Invest New Drugs 2009b;28:35-48.

Spencer JPE, Jenner A, Aruoma OI. Intense oxidative DNA damage promoted by L-DOPA and its metabolites, implications for neurodegenerative disease. FEBS Lett 1994;353:246-50.

Velioglu YS, Mazza G, Gao L, Oomah BD. Antioxidant activity and total phenolics in selected fruits, vegetables and grain products. J Agric Food Chem 1998;46:4113â€7.

Takabe W, Niki E, Uchida K, Yamada S, Satoh K, Noguchi N. Oxidative stress promotes the development of transformation: Involvement of a potent mutagenic lipid peroxidation product, acrolein. Carcinogenesis 2001;22:935-41.

Atmani D, Chaher N, Berboucha M, Ayouni K, Lounis H, Boudaoud H, et al. Antioxidant capacity and phenol content of selected algerian medicinal plants. Food Chem 2009;112:303-9.

Ruberto G, Baratta MT, Deans SG, Dorman HD. Antioxidant and antimicrobial activity of foeniculum vulgare and crithmum maririmum essential oils. Planta Med 2000;66:687–93.

Published

06-10-2015

How to Cite

Asha, K. R., H. G. Rohitkumar, K. B. Gudasi, and G. M. A. Rao. “IN VITRO CYTOTOXICITY AND FREE RADICAL SCAVENGING POTENTIAL OF ETHYL PYRUVATE DERIVED COPPER COMPLEXES OF THIOSEMICARBAZONE”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 13, Oct. 2015, pp. 128-32, https://journals.innovareacademics.in/index.php/ijpps/article/view/7515.