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Synthesis and Anticancer Potential of New Hydroxamic Acid Derivatives as Chemotherapeutic Agents

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Abstract

Histone deacetylase (HDAC) inhibitors have been shown to induce differentiation, cell cycle arrest, and apoptosis due to their low toxicity, inhibiting migration, invasion, and angiogenesis in many cancer cells. Studies show that hydroxamic acids are generally used as anticancers. For this reason, it is aimed to synthesize new derivatives of hydroxamic acids, to examine the anticancer properties of these candidate inhibitors, and to investigate the inhibition effects on some enzymes that cause multidrug resistance in cancer cells. For this reason, new (4-amino-2-methoxy benzohydroxamic acid (a), 4-amino-3-methyl benzohydroxamic acid (b), 3-amino-5-methyl benzohydroxamic acid (c)) amino benzohydroxamic acid derivatives were synthesized in this study. The effects on healthy fibroblast, lung (A549), and cervical (HeLa) cancer cells were investigated. In addition, their effects on TRXR1, GST, and GR activities, which are important for the development of chemotherapeutic strategies, were also examined. It was determined that molecule b was the most effective molecule in HeLa cancer cells with the lowest IC50 value of 0.54. It was determined that molecule c was the most effective molecules for A549 and HeLa cancer cells, with the lowest IC50 values of 0.78 mM and 0.25 mM, respectively. It was determined that b and c molecules directed cancer cells to necrosis rather than apoptosis. c molecule showed anticancer effect in A549 and HeLa cancer cells. It was found that molecule c significantly suppressed both GR and TRXR1 activities. In GST activities, however, inhibitors did not have a significant effect on cancer cells.

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References

  1. World Health Organization. (2020). International Agency for Research on Cancer. Retrieved from https://gco.iarc.fr/

  2. Fitzmaurice, C., Dicker, D., Pain, A., Hamavid, H., Moradi-Lakeh, M., MacIntyre, M. F., & Naghavi, M. (2015). The global burden of cancer 2013. JAMA Oncology, 1(4), 505. https://doi.org/10.1001/jamaoncol.2015.0735

    Article  PubMed  Google Scholar 

  3. Pavlopoulou, A., Spandidos, D. A., & Michalopoulos, I. (2015). Human cancer databases (Review). Oncology Reports, 33(1), 3–18. https://doi.org/10.3892/or.2014.3579

    Article  PubMed  CAS  Google Scholar 

  4. Baykara, O. (2016). Current modalities in treatment of cancer. Balıkesır Health Sciences Journal, 5(3), 154–165. https://doi.org/10.5505/bsbd.2016.93823

    Article  Google Scholar 

  5. Hong, J.-M., Suh, S.-S., Kim, T., Kim, J., Han, S., Youn, U., & Kim, I.-C. (2018). Anti-cancer activity of lobaric acid and lobarstin extracted from the antarctic lichen Stereocaulon alpnum. Molecules, 23(3), 658. https://doi.org/10.3390/molecules23030658

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006). Targeting multidrug resistance in cancer. Nature Reviews Drug Discovery, 5(3), 219–234. https://doi.org/10.1038/nrd1984

    Article  PubMed  CAS  Google Scholar 

  7. Bukowski, K., Kciuk, M., & Kontek, R. (2020). Mechanisms of multidrug resistance in cancer chemotherapy. International Journal of Molecular Sciences, 21(9), 3233. https://doi.org/10.3390/ijms21093233

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Çalışkan, B., Öztürk Kesebir, A., Demir, Y., & Akyol Salman, I. (2022). The effect of brimonidine and proparacaine on metabolic enzymes: glucose‐6‐phosphate dehydrogenase, 6‐phosphogluconate dehydrogenase, and glutathione reductase. Biotechnology and Applied Biochemistry, 69(1), 281–288.

  9. Ceylan, H., Demir, Y., & Beydemir, Ş. (2019). Inhibitory effects of usnic and carnosic acid on some metabolic enzymes: an in vitro study. Protein and Peptide Letters, 26(5), 364–370.

  10. Zimmermann, A. K., Loucks, F. A., Schroeder, E. K., Bouchard, R. J., Tyler, K. L., & Linseman, D. A. (2007). Glutathione binding to the Bcl-2 homology-3 domain groove. Journal of Biological Chemistry, 282(40), 29296–29304. https://doi.org/10.1074/jbc.M702853200

    Article  PubMed  CAS  Google Scholar 

  11. Kowaltowski, A. J., & Fiskum, G. (2005). Redox mechanisms of cytoprotection by Bcl-2. Antioxidants & Redox Signaling, 7(3–4), 508–514. https://doi.org/10.1089/ars.2005.7.508

    Article  CAS  Google Scholar 

  12. Ballatori, N., Krance, S. M., Notenboom, S., Shi, S., Tieu, K., & Hammond, C. L. (2009). Glutathione dysregulation and the etiology and progression of human diseases. Biological Chemistry, 390(3), 191–214. https://doi.org/10.1515/BC.2009.033

  13. Jee, C., Vanoaica, L., Lee, J., Park, B. J., & Ahnn, J. (2005). Thioredoxin is related to life span regulation and oxidative stress response in Caenorhabditis elegans. Genes to Cells, 10(12), 1203–1210. https://doi.org/10.1111/j.1365-2443.2005.00913.x

    Article  PubMed  CAS  Google Scholar 

  14. Duan, D., Zhang, J., Yao, J., Liu, Y., & Fang, J. (2016). Targeting thioredoxin reductase by parthenolide contributes to inducing apoptosis of HeLa cells. Journal of Biological Chemistry, 291(19), 10021–10031. https://doi.org/10.1074/jbc.M115.700591

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. TOPAL, T., Şükrü ÖTER, & Ahmet KORKMAZ.(2009). Melatonin ve kanserle ilişkisi, 19(3), 137–143. Retrieved from https://app.trdizin.gov.tr/makale/T1Rjd01EVTE/melatonin-ve-kanserle-iliskisi-

  16. Yoon, S., & Eom, G. H. (2016). HDAC and HDAC inhibitor: From cancer to cardiovascular diseases. Chonnam Medical Journal, 52(1), 1. https://doi.org/10.4068/cmj.2016.52.1.1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Sanaei, M., & Kavoosi, F. (2019). Histone deacetylases and histone deacetylase inhibitors: Molecular mechanisms of action in various cancers. Advanced Biomedical Research, 8(1), 63. https://doi.org/10.4103/abr.abr_142_19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Seo, J.-Y., Park, Y.-J., Yi, Y.-A., Hwang, J.-Y., Lee, I.-B., Cho, B.-H., & Seo, D.-G. (2015). Epigenetics: General characteristics and implications for oral health. Restorative Dentistry & Endodontics, 40(1), 14. https://doi.org/10.5395/rde.2015.40.1.14

    Article  Google Scholar 

  19. Barneda-Zahonero, B., & Parra, M. (2012). Histone deacetylases and cancer. Molecular Oncology, 6(6), 579–589. https://doi.org/10.1016/j.molonc.2012.07.003

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Chaiyaveij, D., Batsanov, A. S., Fox, M. A., Marder, T. B., & Whiting, A. (2015). An experimental and computational approach to understanding the reactions of acyl nitroso compounds in [4 + 2] cycloadditions. The Journal of Organic Chemistry, 80(19), 9518–9534. https://doi.org/10.1021/acs.joc.5b01470

    Article  PubMed  CAS  Google Scholar 

  21. Yamada, H., Kojo, M., Nakahara, T., Murakami, K., Kakima, T., Ichiba, H., & Fukushima, T. (2012). Development of a fluorescent chelating ligand for scandium ion having a Schiff base moiety. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 90, 72–77. https://doi.org/10.1016/j.saa.2012.01.014

    Article  PubMed  CAS  Google Scholar 

  22. Volz, H. C., Laohachewin, D., Seidel, C., Lasitschka, F., Keilbach, K., Wienbrandt, A. R., & Andrassy, M. (2012). S100A8/A9 aggravates post-ischemic heart failure through activation of RAGE-dependent NF-κB signaling. Basic Research in Cardiology, 107(2), 250. https://doi.org/10.1007/s00395-012-0250-z

    Article  PubMed  CAS  Google Scholar 

  23. You, B. R., & Park, W. H. (2017). Suberoylanilide hydroxamic acid induces thioredoxin1-mediated apoptosis in lung cancer cells via up-regulation of miR-129-5p. Molecular Carcinogenesis, 56(12), 2566–2577. https://doi.org/10.1002/mc.22701

    Article  PubMed  CAS  Google Scholar 

  24. Shankaranarayanan, P., & Nigam, S. (2003). IL-4 induces apoptosis in A549 lung adenocarcinoma cells: Evidence for the pivotal role of 15-hydroxyeicosatetraenoic acid binding to activated peroxisome proliferator-activated receptor γ transcription factor. The Journal of Immunology, 170(2), 887–894. https://doi.org/10.4049/jimmunol.170.2.887

    Article  PubMed  CAS  Google Scholar 

  25. Holmgren, A. (1977). Bovine thioredoxin system.Purification of thioredoxin reductase from calf liver and thymus and studies of its function in disulfide reduction. The Journal of biological chemistry, 252(13), 4600–6. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17603

  26. Holmgren, A., Arner, E., & Bjornstedt, M. (1995).Thioredoxin and thioredoxin reductase. Methods Enzymol, 252, 199–208.

  27. Habig, W. H., Pabst, M. J., & Jakoby, W. B. (1974). Glutathione S-transferases. Journal of Biological Chemistry, 249(22), 7130–7139. https://doi.org/10.1016/S0021-9258(19)42083-8

    Article  PubMed  CAS  Google Scholar 

  28. Carlberg, I., & Mannervik, B. (1975). Purification and characterization of the flavoenzyme glutathione reductase from rat liver. Journal of Biological Chemistry, 250(14), 5475–5480. https://doi.org/10.1016/S0021-9258(19)41206-4

    Article  PubMed  CAS  Google Scholar 

  29. Liu, W., Liang, Y., & Si, X. (2020). Hydroxamic acid hybrids as the potential anticancer agents: An Overview. European Journal of Medicinal Chemistry, 205, 112679. https://doi.org/10.1016/j.ejmech.2020.112679

    Article  PubMed  CAS  Google Scholar 

  30. Li, J.-Q., Chen, C., Yao, M., Sun, L.-Y., Gao, H., Chigan, J., & Yang, K.-W. (2020). Hydroxamic acid with benzenesulfonamide: An effective scaffold for the development of broad-spectrum metallo-β-lactamase inhibitors. Bioorganic Chemistry, 105, 104436. https://doi.org/10.1016/j.bioorg.2020.104436

    Article  PubMed  CAS  Google Scholar 

  31. Chattopadhyay, S. K., Ghosh, S., Sarkar, S., & Bhadra, K. (2019). α, ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA. Beilstein Journal of Organic Chemistry, 15, 2524–2533. https://doi.org/10.3762/bjoc.15.245

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Cao, J., Zang, J., Ma, C., Li, X., Hou, J., Li, J., & Zhang, Y. (2018). Design, synthesis, and biological evaluation of pyrazoline-based hydroxamic acid derivatives as aminopeptidase N (APN) inhibitors. ChemMedChem, 13(5), 431–436. https://doi.org/10.1002/cmdc.201700690

    Article  PubMed  CAS  Google Scholar 

  33. Song, J., Noh, J. H., Lee, J. H., Eun, J. W., Ahn, Y. M., Kim, S. Y., & Nam, S. W. (2005). Increased expression of histone deacetylase 2 is found in human gastric cancer. APMIS, 113(4), 264–268. https://doi.org/10.1111/j.1600-0463.2005.apm_04.x

    Article  PubMed  CAS  Google Scholar 

  34. Halkidou, K., Gaughan, L., Cook, S., Leung, H. Y., Neal, D. E., & Robson, C. N. (2004). Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer. The Prostate, 59(2), 177–189. https://doi.org/10.1002/pros.20022

    Article  PubMed  CAS  Google Scholar 

  35. Zhu, P., Martin, E., Mengwasser, J., Schlag, P., Janssen, K.-P., & Göttlicher, M. (2004). Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell, 5(5), 455–463. https://doi.org/10.1016/S1535-6108(04)00114-X

    Article  PubMed  CAS  Google Scholar 

  36. You, B. R., & Park, W. H. (2010). Suberoyl bishydroxamic acid inhibits the growth of A549 lung cancer cells via caspase-dependent apoptosis. Molecular and Cellular Biochemistry, 344(1–2), 203–210. https://doi.org/10.1007/s11010-010-0543-1

    Article  PubMed  CAS  Google Scholar 

  37. Zhuang, Z., Fei, F., Chen, Y., & Jin, W. (2008). Suberoyl bis-hydroxamic acid induces p53-dependent apoptosis of MCF-7 breast cancer cells. Acta Pharmacologica Sinica, 29(12), 1459–1466. https://doi.org/10.1111/j.1745-7254.2008.00906.x

    Article  PubMed  CAS  Google Scholar 

  38. Ahmad Ganai, S. (2015). Panobinostat: The small molecule metalloenzyme inhibitor with marvelous anticancer activity. Current Topics in Medicinal Chemistry, 16(4), 427–434. https://doi.org/10.2174/1568026615666150813145800

    Article  CAS  Google Scholar 

  39. Martínez-Iglesias, O., Ruiz-Llorente, L., Sánchez-Martínez, R., García, L., Zambrano, A., & Aranda, A. (2008). Histone deacetylase inhibitors: Mechanism of action and therapeutic use in cancer. Clinical and Translational Oncology, 10(7), 395–398. https://doi.org/10.1007/s12094-008-0221-x

    Article  PubMed  CAS  Google Scholar 

  40. Zhou, X., Yang, X.-Y., & Popescu, N. C. (2012). Preclinical evaluation of combined antineoplastic effect of DLC1 tumor suppressor protein and suberoylanilide hydroxamic acid on prostate cancer cells. Biochemical and Biophysical Research Communications, 420(2), 325–330. https://doi.org/10.1016/j.bbrc.2012.02.158

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Zhang, J., Ouyang, W., Li, J., Zhang, D., Yu, Y., Wang, Y., & Huang, C. (2012). Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability. Toxicology and Applied Pharmacology, 263(2), 218–224. https://doi.org/10.1016/j.taap.2012.06.012

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Almenara, J., Rosato, R., & Grant, S. (2002). Synergistic induction of mitochondrial damage and apoptosis in human leukemia cells by flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Leukemia, 16, 1331–1343. https://doi.org/10.1038/sj.leu.2402535

    Article  PubMed  CAS  Google Scholar 

  43. Deroanne, C. F., Bonjean, K., Servotte, S., Devy, L., Colige, A., Clausse, N., & Castronovo, V. (2002). Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene, 21(3), 427–436. https://doi.org/10.1038/sj.onc.1205108

    Article  PubMed  CAS  Google Scholar 

  44. Mottamal, M., Zheng, S., Huang, T., & Wang, G. (2015). Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules, 20(3), 3898–3941. https://doi.org/10.3390/molecules20033898

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Qian, X., Ara, G., Mills, E., LaRochelle, W. J., Lichenstein, H. S., & Jeffers, M. (2008). Activity of the histone deacetylase inhibitor belinostat (PXD101) in preclinical models of prostate cancer. International Journal of Cancer, 122(6), 1400–1410. https://doi.org/10.1002/ijc.23243

    Article  PubMed  CAS  Google Scholar 

  46. Khan, O., & La Thangue, N. B. (2012). HDAC inhibitors in cancer biology: Emerging mechanisms and clinical applications. Immunology & Cell Biology, 90(1), 85–94. https://doi.org/10.1038/icb.2011.100

    Article  CAS  Google Scholar 

  47. Folmer, F., Orlikova, B., Schnekenburger, M., Dicato, M., & Diederich, M. (2010). Naturally occurring regulators of histone acetylation/deacetylation. Current Nutrition & Food Science, 6(1), 78–99. https://doi.org/10.2174/157340110790909581

    Article  CAS  Google Scholar 

  48. Bassett, S., & Barnett, M. (2014). The role of dietary histone deacetylases (HDACs) inhibitors in health and disease. Nutrients, 6(10), 4273–4301. https://doi.org/10.3390/nu6104273

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Losson, H., Schnekenburger, M., Dicato, M., & Diederich, M. (2016). Natural compound histone deacetylase inhibitors (HDACi): Synergy with inflammatory signaling pathway modulators and clinical applications in cancer. Molecules, 21(11), 1608. https://doi.org/10.3390/molecules21111608

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Akone, S. H., Ntie-Kang, F., Stuhldreier, F., Ewonkem, M. B., Noah, A. M., Mouelle, S. E. M., & Müller, R. (2020). Natural products impacting DNA methyltransferases and histone deacetylases. Frontiers in Pharmacology, 11, 992.

  51. Myzak, M. C., Karplus, P. A., Chung, F.-L., & Dashwood, R. H. (2004). A novel mechanism of chemoprotection by sulforaphane. Cancer Research, 64(16), 5767–5774. https://doi.org/10.1158/0008-5472.CAN-04-1326

    Article  PubMed  CAS  Google Scholar 

  52. Darkin-Rattray, S. J., Gurnett, A. M., Myers, R. W., Dulski, P. M., Crumley, T. M., Allocco, J. J., & Schmatz, D. M. (1996). Apicidin: A novel antiprotozoal agent that inhibits parasite histone deacetylase. Proceedings of the National Academy of Sciences, 93(23), 13143–13147. https://doi.org/10.1073/pnas.93.23.13143

    Article  CAS  Google Scholar 

  53. Liu, J., Wang, T., Wang, X., Luo, L., Guo, J., Peng, Y., & Ling, Y. (2017). Development of novel β-carboline-based hydroxamate derivatives as HDAC inhibitors with DNA damage and apoptosis inducing abilities. MedChemComm, 8(6), 1213–1219. https://doi.org/10.1039/C6MD00681G

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Reddy, N. D., Shoja, M. H., Biswas, S., Nayak, P. G., Kumar, N., & Rao, C. M. (2016). An appraisal of cinnamyl sulfonamide hydroxamate derivatives (HDAC inhibitors) for anti-cancer, anti-angiogenic and anti-metastatic activities in human cancer cells. Chemico-Biological Interactions, 253, 112–124. https://doi.org/10.1016/j.cbi.2016.05.008

    Article  PubMed  CAS  Google Scholar 

  55. Zhang, J.-F., Li, M., Miao, J.-Y., & Zhao, B.-X. (2014). Biological activities of novel pyrazolyl hydroxamic acid derivatives against human lung cancer cell line A549. European Journal of Medicinal Chemistry, 83, 516–525. https://doi.org/10.1016/j.ejmech.2014.06.065

    Article  PubMed  CAS  Google Scholar 

  56. Lee, S., Shinji, C., Ogura, K., Shimizu, M., Maeda, S., Sato, M., & Miyachi, H. (2007). Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. Bioorganic & Medicinal Chemistry Letters, 17(17), 4895–4900. https://doi.org/10.1016/j.bmcl.2007.06.038

    Article  CAS  Google Scholar 

  57. Shi, X.-Y., Ding, W., Li, T.-Q., Zhang, Y.-X., & Zhao, S.-C. (2017). Histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), induces apoptosis in prostate cancer cell lines via the Akt/FOXO3a signaling pathway. Medical Science Monitor, 23, 5793–5802. https://doi.org/10.12659/MSM.904597

    Article  PubMed  PubMed Central  Google Scholar 

  58. You, B. R., & Park, W. H. (2014). Suberoylanilide hydroxamic acid-induced HeLa cell death is closely correlated with oxidative stress and thioredoxin 1 levels. International Journal of Oncology, 44(5), 1745–1755. https://doi.org/10.3892/ijo.2014.2337

    Article  PubMed  CAS  Google Scholar 

  59. Librizzi, M., Longo, A., Chiarelli, R., Amin, J., Spencer, J., & Luparello, C. (2012). Cytotoxic effects of Jay Amin hydroxamic acid (JAHA), a ferrocene-based class i histone deacetylase inhibitor, on triple-negative MDA-MB231 breast cancer cells. Chemical Research in Toxicology, 25(11), 2608–2616. https://doi.org/10.1021/tx300376h

    Article  PubMed  CAS  Google Scholar 

  60. Ning, L., Jaskula-Sztul, R., Kunnimalaiyaan, M., & Chen, H. (2008). Suberoyl bishydroxamic acid activates notch1 signaling and suppresses tumor progression in an animal model of medullary thyroid carcinoma. Annals of Surgical Oncology, 15(9), 2600–2605. https://doi.org/10.1245/s10434-008-0006-z

    Article  PubMed  PubMed Central  Google Scholar 

  61. Han, H., Li, J., Feng, X., Zhou, H., Guo, S., & Zhou, W. (2017). Autophagy-related genes are induced by histone deacetylase inhibitor suberoylanilide hydroxamic acid via the activation of cathepsin B in human breast cancer cells. Oncotarget, 8(32), 53352–53365. https://doi.org/10.18632/oncotarget.18410

    Article  PubMed  PubMed Central  Google Scholar 

  62. Wu, G., Fang, Y.-Z., Yang, S., Lupton, J. R., & Turner, N. D. (2004). Glutathione metabolism and its implications for health. The Journal of Nutrition, 134(3), 489–492. https://doi.org/10.1093/jn/134.3.489

    Article  PubMed  CAS  Google Scholar 

  63. Arnér, E. S. (2020). Perspectives of TrxR1-based cancer therapies. In Oxidative stress (pp. 639–667). Academic Press.

  64. Branco, V., Godinho-Santos, A., Gonçalves, J., Lu, J., Holmgren, A., & Carvalho, C. (2014). Mitochondrial thioredoxin reductase inhibition, selenium status, and Nrf-2 activation are determinant factors modulating the toxicity of mercury compounds. Free Radical Biology and Medicine, 73, 95–105. https://doi.org/10.1016/j.freeradbiomed.2014.04.030

    Article  PubMed  CAS  Google Scholar 

  65. Jia, J.-J., Geng, W.-S., Wang, Z.-Q., Chen, L., & Zeng, X.-S. (2019). The role of thioredoxin system in cancer: Strategy for cancer therapy. Cancer Chemotherapy and Pharmacology, 84(3), 453–470. https://doi.org/10.1007/s00280-019-03869-4

    Article  PubMed  CAS  Google Scholar 

  66. Ouyang, Y., Peng, Y., Li, J., Holmgren, A., & Lu, J. (2018). Modulation of thiol-dependent redox system by metal ions via thioredoxin and glutaredoxin systems. Metallomics, 10(2), 218–228. https://doi.org/10.1039/C7MT00327G

    Article  PubMed  CAS  Google Scholar 

  67. Tonissen, K. F., & Di Trapani, G. (2009). Thioredoxin system inhibitors as mediators of apoptosis for cancer therapy. Molecular Nutrition & Food Research, 53(1), 87–103. https://doi.org/10.1002/mnfr.200700492

    Article  CAS  Google Scholar 

  68. Özaslan, M. S., Demir, Y., Aslan, H. E., Beydemir, Ş., & Küfrevioğlu, Ö. İ. (2018). Evaluation of chalcones as inhibitors of glutathione S‐transferase. Journal of Biochemical and Molecular Toxicology, 32(5), e22047.

  69. Özaslan, M. S., Demir, Y., Küfrevioğlu, O. I., & Çiftci, M. (2017). Some metals inhibit the glutathione S‐transferase from Van Lake fish gills. Journal of Biochemical and Molecular Toxicology, 31(11), e21967.

  70. Meister, A., & Anderson, M. E. (1983). GLUTATHIONE. Annual Review of Biochemistry, 52(1), 711–760. https://doi.org/10.1146/annurev.bi.52.070183.003431

    Article  PubMed  CAS  Google Scholar 

  71. Siegel, R. L., Miller, K. D., & Jemal, A. (2015). Cancer statistics, 2015. CA: A Cancer Journal for Clinicians, 65(1), 5–29. https://doi.org/10.3322/caac.21254

    Article  PubMed  Google Scholar 

  72. Tew, K. D. (1994). Glutathione-associated enzymes in anticancer drug resistance. Cancer research, 54(16), 4313–20. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8044778

  73. Harrison, D. J., Kharbanda, R., Bishop, D., McLelland, L. I., & Hayes, J. D. (1989). Glutathione S-transferase isoenzymes in human renal carcinoma demonstrated by immunohistochemistry. Carcinogenesis, 10(7), 1257–1260. https://doi.org/10.1093/carcin/10.7.1257

    Article  PubMed  CAS  Google Scholar 

  74. Tidefelt, U., Elmhorn-Rosenborg, A., Paul, C., Hao, X. Y., Mannervik, B., & Eriksson, L. C. (1992). Expression of glutathione transferase pi as a predictor for treatment results at different stages of acute nonlymphoblastic leukemia. Cancer research, 52(12), 3281–5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1596886

  75. Green, J., Robertson, L., & Clark, A. (1993). Glutathione S-transferase expression in benign and malignant ovarian tumours. British Journal of Cancer, 68(2), 235–239. https://doi.org/10.1038/bjc.1993.321

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Gilbert, L., Elwood, L. J., Merino, M., Masood, S., Barnes, R., Steinberg, S. M., & Moscow, J. A. (1993). A pilot study of pi-class glutathione S-transferase expression in breast cancer: Correlation with estrogen receptor expression and prognosis in node-negative breast cancer. Journal of Clinical Oncology, 11(1), 49–58. https://doi.org/10.1200/JCO.1993.11.1.49

    Article  PubMed  CAS  Google Scholar 

  77. Grignon, D. J., Abdel-Malak, M., Mertens, W. C., Sakr, W. A., & Shepherd, R. R. (1994). Glutathione S-transferase expression in renal cell carcinoma: A new marker of differentiation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 7(2), 186–9. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8008741

  78. Hamada, S.-I., Kamada, M., Furumoto, H., Hirao, T., & Aono, T. (1994). Expression of glutathione S-transferase-π in human ovarian cancer as an indicator of resistance to chemotherapy. Gynecologic Oncology, 52(3), 313–319. https://doi.org/10.1006/gyno.1994.1055

    Article  PubMed  CAS  Google Scholar 

  79. Yang, P., Ebbert, J. O., Sun, Z., & Weinshilboum, R. M. (2006). Role of the glutathione metabolic pathway in lung cancer treatment and prognosis: A review. Journal of Clinical Oncology, 24(11), 1761–1769. https://doi.org/10.1200/JCO.2005.02.7110

    Article  PubMed  CAS  Google Scholar 

  80. Estrela, J. M., Ortega, A., & Obrador, E. (2006). Glutathione in cancer biology and therapy. Critical Reviews in Clinical Laboratory Sciences, 43(2), 143–181. https://doi.org/10.1080/10408360500523878

    Article  PubMed  CAS  Google Scholar 

  81. Türkan, F., Huyut, Z., Demir, Y., Ertaş, F., & Beydemir, Ş. (2019). The effects of some cephalosporins on acetylcholinesterase and glutathione S-transferase: an in vivo and in vitro study. Archives of Physiology and Biochemistry, 125(3), 235–243.

  82. Türkeş, C., Demir, Y., & Beydemir, Ş. (2021). Infection medications: Assessment in‐vitro glutathione S‐Transferase inhibition and molecular docking study. ChemistrySelect, 6(43), 11915–11924.

  83. Türkeş, C., Kesebir Öztürk, A., Demir, Y., Küfrevioğlu, Ö. İ., & Beydemir, Ş. (2021). Calcium channel blockers: The effect of glutathione S‐Transferase enzyme activity and molecular docking studies. ChemistrySelect, 6(40), 11137–11143.

  84. Özaslan, M. S., Demir, Y., Aksoy, M., Küfrevioğlu, Ö. I., & Beydemir, Ş. (2018). Inhibition effects of pesticides on glutathione‐S‐transferase enzyme activity of Van Lake fish liver. Journal of Biochemical and Molecular Toxicology, 32(9), e22196.

  85. Pias, E. K., & Yee Aw, T. (2002). Apoptosis in mitotic competent undifferentiated cells is induced by cellular redox imbalance independent of reactive oxygen species production. The FASEB Journal, 16(8), 781–790. https://doi.org/10.1096/fj.01-0784com

    Article  PubMed  CAS  Google Scholar 

  86. Beutler, E. (1969). Effect of flavin compounds on glutathione reductase activity: In vivo and in vitro studies. Journal of Clinical Investigation, 48(10), 1957–1966. https://doi.org/10.1172/JCI106162

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Lu, J., & Holmgren, A. (2014). The thioredoxin antioxidant system. Free Radical Biology and Medicine, 66, 75–87. https://doi.org/10.1016/j.freeradbiomed.2013.07.036

    Article  PubMed  CAS  Google Scholar 

  88. Liu, Y., Hyde, A. S., Simpson, M. A., & Barycki, J. J. (2014). Emerging regulatory paradigms in glutathione metabolism. Advances in Cancer Research, 122, 69–101.

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Authors and Affiliations

  1. Faculty of Science, Department of Chemistry, Atatürk University, Erzurum, 25240, Turkey

    Işıl Nihan Korkmaz & Hasan Özdemir

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  1. Işıl Nihan Korkmaz
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  2. Hasan Özdemir
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Contributions

INK carried out experiments to determine in vitro cytotoxicity and evaluation of the anti-cancer potency. INK and HO planned the work, interpreted, consolidated the data, and wrote the manuscript. HO coordinated and supervised the work. All authors read and approved the final manuscript. The authors have no conficts of interest.

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Correspondence to Hasan Özdemir.

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Korkmaz, I.N., Özdemir, H. Synthesis and Anticancer Potential of New Hydroxamic Acid Derivatives as Chemotherapeutic Agents. Appl Biochem Biotechnol 194, 6349–6366 (2022). https://doi.org/10.1007/s12010-022-04107-z

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