AccScience Publishing / ITPS / Volume 6 / Issue 2 / DOI: 10.36922/itps.0618
Cite this article
81
Download
1700
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Evaluation of genotoxicity of (4-fluorophenyl) thiazolidin-4-one in CHO-K1 cells

Jhansi Mamilla1† Kalpana Javvaji1,3† Kavya Lekha Sunkara1 Umesh B. Kosurkar2 Ravindra M. Kumbhare2,3* Sunil Misra1,3*
Show Less
1 Genetic Toxicology Lab, Applied Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India
2 Department of Fluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India
3 Academy of Scientific and Innovative Research, Ghaziabad, India
INNOSC Theranostics and Pharmacological Sciences 2023, 6(2), 0618 https://doi.org/10.36922/itps.0618
Submitted: 18 April 2023 | Accepted: 18 July 2023 | Published: 7 August 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

4-thiazolidinones are five-membered heterocyclic ring compounds with diverse pharmacological impacts. In a previous study, we reported a series of newly synthesized derivatives of 4-thiazolidinones with different functional groups, which exhibited anticancer activity against ovarian (SKOV3) and cervical (HeLa) cancer cell lines. Among these derivatives, (4-fluorophenyl) thiazolidin-4-one (4-TH) demonstrated potent cytotoxic activity against SKOV3, with an IC50 value of 12.3 μM. However, it was also found to be extremely toxic to normal cells (CHO-K1) with an IC50 of 7.5 μM. Before considering its use in cancer research, it is crucial to gain a comprehensive understanding of its potential genotoxic effects on normal cells. In this study, we aimed to assess the in vitro cytogenetic toxicity of 4-TH using normal Chinese hamster ovary cells (CHO-K1). Referring to the IC50 of 4-TH, we selected three sub-lethal concentrations (2, 5, and 7.5 μM) and treated CHO-K1 cells for 24 h (one cell cycle duration) to estimate its dose-dependent induction of chromosome aberrations, and examine the effect of 4-TH on cell division, micronucleus induction potential and cell cycle arrest properties following standard protocols. The results showed that 4-TH was highly toxic to normal cells, as all three sublethal concentrations caused a statistically significant increase in the number of chromosomal aberrations (P < 0.001), formation of micronuclei (P < 0.01), and changes in the rate of cell division (mitotic index) (P < 0.05) compared to control. In addition, there was a significant increase in the number of cells in the G1 phase, indicating that all concentrations of 4-TH tested induced apoptosis. The evaluation of the cytotoxic, clastogenic, and aneugenic properties of 4-TH, a potent cytotoxic agent, will undoubtedly provide critical information for determining its safety and potential as an anticancer drug.

Keywords
Cytotoxicity
Chromosome aberration
Mitotic index
Micronucleus
Cell cycle
Funding
None.
Conflict of interest
All the authors declare that they have no competing interests.
References
  1. Brown FC, 1961, 4-Thiazolidinones. Chem Rev, 61: 463–521.

 

  1. Jain AK, Vaidya A, Ravichandran V, et al., 2012, Recent developments and biological activities of thiazolidinone derivatives: A review. Bioog Med Chem, 20: 3378–3395. https://doi.org/10.1016/j.bmc.2012.03.069

 

  1. Tripathi AC, Gupta SJ, Fatima G, et al., 2014, 4-Thiazolidinones: The advances continue. Eur J Med Chem, 72, 52–77. https://doi.org/10.1016/j.ejmech.2013.11.017

 

  1. Thomas B, LS A, Harindran J, 2014, Novel Mannich bases of 4-thiazolidinone derivatives as antitubercular agents. Int J Res Pharm Chem, 4: 351–359. https://doi.org/10.1016/j.jsps.2010.05.002

 

  1. Patel NB, Shaikh FM, 2010, Synthesis and antimicrobial activity of new 4-thiazolidinone derivatives containing 2-amino-6- methoxybenzothiazole. Saudi Pharm J, 18: 129–136.

 

  1. Vicini P, Geronikaki A, Anastasia K, et al., 2006, Synthesis and antimicrobial activity of novel 2-thiazolylimino-5-arylidene- 4-thiazolidinones. Bioorg Med Chem, 14: 3859–3864. https://doi.org/10.1016/j.bmc.2006.01.043

 

  1. Ulusoy N, Ergenç N, Ekinci AC, et al., 1996, Synthesis and anticonvulsant activity of some new arylidenehydrazides and 4-thiazolidinones. Mon Chem/Chem Mon, 127: 1197–1202. https://doi.org/10.1007/bf00844695

 

  1. Archana, Srivastava VK, Kumar A, 2002, Synthesis of newer thiadiazolyl and thiazolidinonyl quinazolin-4 3H-ones as potential anticonvulsant agents. Eur J Med Chem, 37: 873–882. https://doi.org/10.1016/s0223-5234(02)01389-2

 

  1. Shiradkar MR, Ghodake M, Bothara KG, et al., 2007, Synthesis and anticonvulsant activity of clubbed thiazolidinone-barbituric acid and thiazolidinone-triazole derivatives. Arkivoc, 14: 58-74. https://doi.org/10.3998/ark.5550190.0008.e08

 

  1. Ottana R, Maccari R, Barreca ML, et al., 2005, 5-Arylidene- 2-imino-4-thiazolidinones: Design and synthesis of novel anti-inflammatory agents. Bioorg Med Chem, 13: 4243–4252. https://doi.org/10.1016/j.bmc.2005.04.058

 

  1. Boyd MR, Paull KD, 1995, Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev Res, 34: 91–109. https://doi.org/10.1002/ddr.430340203

 

  1. Carter PH, Scherle PA, Muckelbauer JA, et al., 2001, Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-alpha. Proc Natl Acad Sci, 98: 11879–11884. https://doi.org/10.1073/pnas.211178398

 

  1. Cutshall NS, O’Day C, Prezhdo M, 2005, Rhodanine derivatives as inhibitors of JSP-1. Bioorg Med Chem Lett, 15: 3374–3379. https://doi.org/10.1016/j.bmcl.2005.05.034

 

  1. Look GC, Schullek JR, Holmes CP, et al., 1996, The identification of cyclooxygenase-1 inhibitors from 4-thiazolidinone combinatorial libraries. Bioorg Med Chem Let, 6: 707–712. https://doi.org/10.1016/0960-894x(96)00097-2

 

  1. Barreca ML, Chimirri A, De Luca L, et al., 2001, Discovery of 2,3-diaryl-1,3-thiazolidin-4-ones as potent anti-HIV-1 agents. Bioorg Med Chem Lett, 11: 1793–1796. https://doi.org/10.1016/s0960-894x(01)00304-3

 

  1. Rao A, Carbone A, Chimirri A, et al., 2002, Synthesis and anti-HIV activity of 2,3-diaryl-1,3-thiazolidin-4-(thi)one derivatives. Il Farmaco, 57: 747–751. https://doi.org/10.1016/S0014-827X(02)01268-5

 

  1. Rao A, Balzarini J, Carbone A, et al., 2004, Synthesis of new 2,3-diaryl-1,3-thiazolidin-4-ones as anti-HIV agents. Il Farmaco, 59: 33–39. https://doi.org/10.1016/j.farmac.2003.09.001

 

  1. Balzarini J, Orzeszko B, Maurin JK, et al., 2007, Synthesis and anti-HIV studies of 2-adamantyl-substituted thiazolidin-4- ones. Eur J Med Chem, 42: 993–1003. https://doi.org/10.1016/j.ejmech.2007.01.003

 

  1. Rao A, Chimirri A, Ferro S, et al., 2004, Microwave-induced synthesis of benzimidazole and thiazolidinone derivatives as HIV-1 RT inhibitors. Arkivoc, 5: 147–155. https://doi.org/10.3998/ark.5550190.0005.514

 

  1. Ravichandran V, Kumar BP, Sankar S, 2009, Predicting anti- HIV activity of 1,3,4-thiazolidinone derivaties: 3D-QSAR approach. Eur J Med Chem, 44: 1180–1187. https://doi.org/10.1016/j.ejmech.2008.05.036

 

  1. Mosula L, Zimenkovsky B, Havrylyuk D, et al., 2009, Synthesis and antitumor activity of novel 2-thioxo-4- thiazolidinones with benzothiazole moieties. Farmacia, 57: 321–330.

 

  1. Dua R, Shrivastava S, Sonwane SK, et al., 2011, Pharmacological significance of synthetic heterocycles scaffold: A review. Adv Biol Res, 5: 20–144.

 

  1. Zahradnik M, 1983, The Production and Application of Fluorescent Brightening Agents. Translated by Wilkinson Procharzka ZF. Chichester: Wiley-Interscience, p147.

 

  1. Naganna MG, Rohini YR, 2014, Synthesis antimicrobial and antioxidant evaluation of 3-(2-(4-fluorobenzylthio) pyrimidin-4-yl-amino)-2-(3-substituted phenyl) thiazolidin-4-ones. World J Pharm Pharm Sci, 3: 1094–1109.

 

  1. Liu HL, Li Z, Anthonsen T, 2000, Synthesis and fungicidal activity of 2-imino-3-(4-arylthiazol-2-yl)-thiazolidin-4-ones and their 5-arylidene derivatives. Molecules, 5: 1055–1061. https://doi.org/10.3390/50901055

 

  1. Radin NS, 2008, Drug design: Hiding in full view. Drug Dev Res, 69: 15–25. https://doi.org/10.1002/ddr.20223

 

  1. Thomas AB, Nanda RK, Kothapalli LP, et al., 2013, Synthesis, biological activity, molecular modelling studies and 3D-QSAR Investigations of N-[2-(aryl/substituted aryl)-4- oxo-1, 3-thiazolidin-3-yl] pyridine-4-carboxamides. Open Conf Proc J, 4: 99–112. https://doi.org/10.2174/2210289201304010099

 

  1. Taranalli AD, Bhat AR, Srinivas S, et al., 2008, Antiinflammatory,analgesic and antipyretic activity of certain thiazolidinones. Indian J Pharm Sci, 70: 159. https://doi.org/10.4103/0250-474X.41448

 

  1. Kosurkar UB, Mamilla J, Dadmal TL, et al., 2023, Synthesis of novel Thiazolidine-4-One derivatives, their cytotoxicity, antifungal properties, molecular docking and molecular dynamics. Rus J Bioorg Chem, 49, 314–323. https://doi.org/10.1134/S1068162023020127

 

  1. Gandhi B, Juliya J, Dileep V, et al., 2021, Antioxidant and biological activities of novel structured monoacylglycerol derivatives with phenolic acids. Eur J Lipid Sci Technol, 123: 2100055. https://doi.org/10.1002/ejlt.202100055

 

  1. Deshpande SS, Veeragoni D, Rachamalla HK, et al., 2022, Anticancer properties of ZnO-Curcumin nanocomposite against melanoma cancer and its genotoxicity profiling. J Drug Deliv Sci Tech, 75: 103703. https://doi.org/10.1016/j.jddst.2022.103703

 

  1. Choudante PC, Nethi SK, Díaz-García D, et al., 2022, Tin-loaded mesoporous silica nanoparticles: Antineoplastic properties and genotoxicity assessment. Biomater Adv, 137: 212819. https://doi.org/10.1016/j.bioadv.2022.212819

 

  1. Javvaji K, Mamilla J, Kongari L, et al., 2023, In vitro cytogenetic toxicity and cell cycle arrest profiling of fluorinated trifluoromethyl 4-Thiazolidinone on CHO-K1 cells. Arch Clin Toxicol, 5: 1–8. https://doi.org/10.46439/toxicology.5.018

 

  1. Bhat M, Poojary B, Kalal BS, et al., 2018, Synthesis and evaluation of thiazolidinone-pyrazole conjugates as anticancer and antimicrobial agents. Future Med Chem, 10: 1017–1036. https://doi.org/10.4155/fmc-2017-0191

 

  1. Djukic M, Fesatidou M, Xenikakis I, et al., 2018, In vitro antioxidant activity of thiazolidinone derivatives of 1,3-thiazole and 1,3,4-thiadiazole. Chem Biol Interact, 286: 119–131. https://doi.org/10.1016/j.cbi.2018.03.013

 

  1. Dillehay LE, Denstman SC, Williams JR, 1987, Cell cycle dependence of sister chromatid exchange induction by DNA topoisomerase II inhibitors in Chinese hamster V79 cells. Can Res, 47: 206–209.

 

  1. Çelik A, Eke D, 2011, The assessment of cytotoxicity and genotoxicity of tetracycline antibiotic in human blood lymphocytes using CBMN and SCE analysis, in vitro. Int J Hum Gen, 11: 23–29. https://doi.org/10.1080/09723757.2011.11886119

 

  1. Hagmar L, Bonassi S, Strömberg U, et al., 1998, Chromosomal aberrations in lymphocytes predict human cancer: A report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Can Res, 58: 4117–4121.
Share
Back to top
INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Print ISSN: 2705-0734, Published by AccScience Publishing