IN VITRO CYTOTOXICITY AND FREE RADICAL SCAVENGING POTENTIAL OF ETHYL PYRUVATE DERIVED COPPER COMPLEXES OF THIOSEMICARBAZONE
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.
2. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation and cancer: How are they linked? Free Radic Biol Med 2010;49:1603â€“16.
3. Lakshmi SV, Padmaja G, Kuppuswamy P, Kutala VK. Oxidative stress in cardiovascular disease. Indian J Biochem Biophys 2009;46:421-40.
4. Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes 1991;40:405-12.
5. Perry G, Cash AD, Smith MA. Alzheimer disease and oxidative stress. J Biomed Biotechnol 2002;2:120â€“3.
6. Hussain SP, Hofseth LJ, Harris CC. Radical causes of cancer. Nat Rev Cancer 2003;3:276-86.
7. Cerutti PA, Trump BF. Inflammation and oxidative stress in carcinogenesis. Cancer Cells 1991;3:1-7.
8. 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]
9. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010;4:118â€“26.
10. 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.
11. 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;27:1278â€“85.
12. 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.
13. Kappus H. Overview of enzyme systems involved in bio-reduction of drugs and in redox cycling. Biochem Pharmacol 19861;35:1â€“6.
14. 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;65:157â€“73.
15. 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;18:4131â€“40.
16. 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;430:216â€“24.
17. Mosmann TJ. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Immunol Methods 1983;65:55â€“63.
18. 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;582:4066â€“76.
19. 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.
20. Puneeth HR, Sharada AC. Antioxidant and hypoglycemic effects of curcumin pyrazole derivatives. Int J Pharm Pharm Sci 2015;7:244â€“9.
21. Halliwell B, Gutteridge JMC, Aruoma OI. The deoxyribose method: a simple â€˜test tubeâ€™ assay for determination of rates constants for reactions of hydroxyl radical. Anal Biochem 1987;165:215-24.
22. Ohkawa H, Ohishi N, Yagi K. Assay of lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351â€“8.
23. Vara D, Pula G. Reactive oxygen species: physiological roles in the regulation of vascular cells. Curr Mol Med 2014;14:1103â€“25.
24. Liou GY, Storz P. Reactive oxygen species in cancer. Free Radic Res 2010;44:479â€“96.
25. Wang J, Yi J. Cancer cell killing via ROS: To increase or decrease, that is a question. Cancer Biol Ther 2010;7:1875â€“84.
26. Rahman K. Studies on free radicals, antioxidants, and co-factors. Clin Interventions Aging 2007;2:219â€“36.
27. Wang D, Lippard SJ. Cellular processing of platinum anticancer drugs. Nat Rev Drug Discovery 2005;4:307â€“20.
28. 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;147:117â€“23.
29. 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;12:1352â€“66.
30. 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]
31. 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;129:17â€“26.
32. 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;5:120â€“5.
33. 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;18:8812â€“36.
34. Ingo Ott. On the medicinal chemistry of gold complexes as anticancer drugs. Coord Chem Rev 2009;253:1670â€“81.
35. Smith FE. Tetrazolium Salt. Science 1951;113:751â€“4.
36. 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.
37. 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.
38. 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.
39. 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.
40. 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.
41. Ruberto G, Baratta MT, Deans SG, Dorman HD. Antioxidant and antimicrobial activity of foeniculum vulgare and crithmum maririmum essential oils. Planta Med 2000;66:687â€“93.