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Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers

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Abstract

In the present study, the various 28 hybrid molecules containing hydrazone and sulfonate moieties were synthesized and characterized by FTIR, 1H-NMR, 13C-NMR spectroscopy and LC-MS spectrometry, besides elemental analysis. The compounds were evaluated for their antiproliferative effects against six cancer cell lines, namely A549 (non-small cell lung cancer), MCF-7 (breast cancer), HT-29 (colorectal adenocarcinoma cancer), PC-3 (androgen-independent prostate adenocarcinoma), Hep3B (hepatocellular carcinoma cancer), and HeLa (epitheloid cervix carcinoma cancer). Among all the target compounds, compounds 4g and 4h exhibited more promising effects on MCF-7 cell lines (IC50 = 17.8 μM and 21.2 μM, respectively) with high selectivity. Further mechanistic studies proposed that compounds 4g and 4h induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating caspase-9 and caspase-3. The results have been encouraging enough to merit further investigation.

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References

  1. Rollas S, Küçükgüzel ŞG. Biological activities of hydrazone derivatives. Molecules. 2007;12:1910–39. https://doi.org/10.1016/j.ejmech.2003.08.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Şenkardeş S, Kaushik-Basu N, Durmaz I, Manvar D, Basu A, Atalay R, et al. Synthesis of novel diflunisal hydrazide-hydrazones as anti-hepatitis C virus agents and hepatocellular carcinoma inhibitors. Eur J Med Chem. 2016;108:301–8. https://doi.org/10.1016/j.ejmech.2015.10.041.

    Article  CAS  PubMed  Google Scholar 

  3. Zhang D, Ma Y, Liu Y, Liu ZP. Synthesis of sulfonylhydrazone- and acylhydrazone-substituted 8-ethoxy-3-nitro-2H-chromenes as potent antiproliferative and apoptosis inducing agents. Arch Pharm. 2014;347:576–88. https://doi.org/10.1002/ardp.201400082.

    Article  CAS  Google Scholar 

  4. Küçükgüzel G, Koç D, Çikla-Süzgün P, Özsavci D, Bingöl-Özakpinar Ö, Mega-Tiber P, et al. Synthesis of tolmetin hydrazide-hydrazones and discovery of a potent apoptosis inducer in colon cancer cells. Arch Pharm. 2015;348:730–42. https://doi.org/10.1002/ardp.201500178.

    Article  CAS  Google Scholar 

  5. Han Mİ, Atalay P, Tunç CÜ, Ünal G, Dayan S, Aydın Ö, et al. Design and synthesis of novel (S)-naproxen hydrazide-hydrazones as potent VEGFR-2 inhibitors and their evaluation in vitro/in vivo breast cancer models. Bioorg Med Chem. 2021;37:116097 https://doi.org/10.1016/j.bmc.2021.116097.

    Article  CAS  PubMed  Google Scholar 

  6. Nechepurenko IV, Shirokova ED, Khvostov MV, Frolova TS, Sinitsyna OI, Maksimov AM, et al. Synthesis, hypolipidemic and antifungal activity of tetrahydroberberrubine sulfonates. Russ Chem Bull. 2019;68:1052–60. https://doi.org/10.1007/s11172-019-2519-y.

    Article  CAS  Google Scholar 

  7. Chen S, Zhang Y, Liu Y, Wang Q. Design, synthesis, acaricidal activities, and structure-activity relationship studies of novel oxazolines containing sulfonate moieties. J Agric Food Chem. 2019;67:13544–9. https://doi.org/10.1021/acs.jafc.9b05547.

    Article  CAS  PubMed  Google Scholar 

  8. Bagul SD, Rajput JD, Patil MM, Bendre RS. Synthesis, characterization and antioxidant activity of carvacrol based sulfonates. Med Chem. 2017;7:294–8. https://doi.org/10.4172/2161-0444.1000470.

    Article  CAS  Google Scholar 

  9. Grindrod S, Suy S, Fallen S, Eto M, Toretsky J, Brown ML. Effects of a fluorescent myosin light chain phosphatase inhibitor on prostate cancer cells. Front Oncol. 2011;1:1–17. https://doi.org/10.3389/fonc.2011.00027.

    Article  Google Scholar 

  10. Fortin S, Charest-Morin X, Turcotte V, Lauvaux C, Lacroix J, Côté MF, et al. Activation of phenyl 4-(2-Oxo-3-Alkylimidazolidin-1-yl)benzenesulfonates prodrugs by CYP1A1 as new antimitotics targeting breast cancer cells. J Med Chem. 2017;60:4963–82. https://doi.org/10.1021/acs.jmedchem.7b00343.

    Article  CAS  PubMed  Google Scholar 

  11. Krueger AB, Dehdashti SJ, Southall N, Marugan JJ, Ferrer M, Li X, et al. Identification of a selective small-molecule inhibitor series targeting the eyes absent 2 (Eya2) phosphatase activity. J Biomol Screen. 2013;18:85–96. https://doi.org/10.1177/1087057112453936.

    Article  CAS  PubMed  Google Scholar 

  12. Dorababu A. Synthesis, pharmacological evaluation and structure-activity relationship of recently discovered enzyme antagonist azoles. Heliyon. 2020;6:e03656. https://doi.org/10.1016/j.heliyon.2020.e03656.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Han Mİ, Bekçi H, Cumaoğlu A, Küçükgüzel G. Synthesis and characterization of 1,2,4-triazole containing hydrazide-hydrazones derived from (S)-naproxen as anticancer agents. Marmara Pharm J. 2018;22:559–69. https://doi.org/10.12991/jrp.2018.98.

    Article  CAS  Google Scholar 

  14. Şenkardeş S, Türe A, Ekrek S, Durak AT, Abbak M, Çevik Ö, et al. Novel 2,6-disubstituted pyridine hydrazones: Synthesis, anticancer activity, docking studies and effects on caspase-3-mediated apoptosis. J Mol Struct. 2021;1223:1–9. https://doi.org/10.1016/j.molstruc.2020.128962.

    Article  CAS  Google Scholar 

  15. Küçükgüzel SG, Mazi A, Sahin F, Öztürk S, Stables J. Synthesis and biological activities of diflunisal hydrazide-hydrazones. Eur J Med Chem. 2003;38:1005–13. https://doi.org/10.1016/j.ejmech.2003.08.004.

    Article  CAS  PubMed  Google Scholar 

  16. Çikla P, Arora P, Basu A, Talele TT, Kaushik-Basu N, Küçükgüzel ŞG. Etodolac thiosemicarbazides: a novel class of hepatitis C virus NS5B polymerase inhibitors. Marmara Pharm J. 2013;17:138–46. https://doi.org/10.12991/201317382.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Amir M, Kumar S. Synthesis and anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities of 3,5-dimethyl pyrazoles, 3-methyl pyrazol-5-ones and 3,5-disubstituted pyrazolines. Indian J Chem Sect B Org Med Chem. 2005;44:2532–7. https://doi.org/10.1002/chin.200615110.

    Article  Google Scholar 

  18. Karakuş S, Rollas S. Synthesis and antimycobacterial activity of some 2-(4-aminophenyl)-5-substituted amino-1,3,4-thiadiazole derivatives and their coupling products. Marmara Pharm J. 2016;20:199–206. https://doi.org/10.12991/mpj.20162013533.

    Article  CAS  Google Scholar 

  19. Khasawneh R, Kornreich R. Synthesis,characterization and anti-inflammatory activity of 5- substituted phenyl-N-(6-(propylthio)-1H-benzo[d]imidazol-2-yl) -1, 3, 4-oxadiazol-2-amines. Pharmacogenomics. 1809;3:781–91.

    Google Scholar 

  20. Şenkardeş S, Han Mİ, Kulabaş N, Abbak M, Çevik Ö, Küçükgüzel İ, et al. Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors. Mol Divers. 2020;24:673–89. https://doi.org/10.1007/s11030-019-09974-z.

    Article  CAS  PubMed  Google Scholar 

  21. Mao PCM, Mouscadet JF, Leh H, Auclair C, Hsu LY. Chemical modification of coumarin dimer and HIV-1 integrase inhibitory activity. Chem Pharm Bull. 2002;50:1634–7. https://doi.org/10.1248/cpb.50.1634.

    Article  CAS  Google Scholar 

  22. Samrin F, Sharma A, Khan IA, Puri S. Synthesis and antibacterial activity of new diaryldiamines. J Heterocycl Chem. 2012;49:1391–7. https://doi.org/10.1002/jhet.1040.

    Article  CAS  Google Scholar 

  23. Aydin S, Kaushik-Basu N, Arora P, Basu A, Nichols DB, Talele TT. et al. Microwave assisted synthesis of some novel flurbiprofen hydrazide hydrazones as anti-HCV NS5B and anticancer agents. Marmara Pharm J. 2013;17:26–34. https://doi.org/10.12991/201317389.

    Article  CAS  Google Scholar 

  24. Nowak G. Protein kinase C-α and ERK1/2 mediate mitochondrial dysfunction, decreases in active Na+ transport, and cisplatin-induced apoptosis in renal cells. J Biol Chem. 2002;277:43377–88. https://doi.org/10.1074/jbc.M206373200.

    Article  CAS  PubMed  Google Scholar 

  25. Utsuro M. Neutron spin interference visibility in tunneling transmission through magnetic resonators. Phys B Condens Matter. 2005;358:232–46. https://doi.org/10.1016/j.physb.2005.01.398.

    Article  CAS  Google Scholar 

  26. Pistritto G, Trisciuoglio D, Ceci C, Alessia G, D’Orazi G. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging. 2016;8:603–19. https://doi.org/10.18632/aging.100934.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kang MH, Reynolds CP. BcI-2 Inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res. 2009;15:1126–32. https://doi.org/10.1158/1078-0432.CCR-08-0144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Taşkin Tok T, Özaşik Ö, Sarigöl D, Uzgören Baran A. Synthesis and molecular modeling studies of naproxen-based acyl hydrazone derivatives. Turkish J Chem. 2015;39:64–83. https://doi.org/10.3906/kim-1401-91.

    Article  CAS  Google Scholar 

  29. Kulabaş N, Özakpinar ÖB, Özsavcı D, Leyssen P, Neyts J, Küçükgüzel İ. Synthesis, characterization and biological evaluation of thioureas, acylthioureas and 4-thiazolidinones as anticancer and antiviral agents. Marmara Pharm J. 2017;21:371–84. https://doi.org/10.12991/marupj.300913.

    Article  Google Scholar 

  30. Bingöl Özakpinar Ö, Türe A, Küçükgüzel İ. Molecular modeling and assessment of cytotoxic and apoptotic potentials of imatinib analogues featuring (Thio)urea motifs in human leukemia and lymphoma cells. J Res Pharm. 2020;24:801–11. https://doi.org/10.35333/jrp.2020.239.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported financially by the Scientific and Technological Research Council of Turkey (TUBITAK) (Project Number: 118S840).

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Authors and Affiliations

  1. Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Marmara University, Maltepe, Başıbüyük, 34854, Istanbul, Turkey

    Sevil Şenkardeş

  2. Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Erciyes University, Talas, 38280, Kayseri, Turkey

    M. İhsan Han

  3. Faculty of Pharmacy, Department of Biochemistry, Marmara University, Maltepe, Başıbüyük, 34854, Istanbul, Turkey

    Merve Gürboğa & Özlem Bingöl Özakpinar

  4. Vocational School of Health Services, Fenerbahçe University, Ataşehir, 34758, Istanbul, Turkey

    Ş. Güniz Küçükgüzel

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  1. Sevil Şenkardeş
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Şenkardeş, S., İhsan Han, M., Gürboğa, M. et al. Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers. Med Chem Res 31, 368–379 (2022). https://doi.org/10.1007/s00044-021-02837-z

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