Advertisement

Synthesis and anticancer activity of chalcone analogues with sulfonyl groups

  • Jovana M. MuškinjaEmail author
  • Adrijana Z. Burmudžija
  • Dejan D. Baskić
  • Suzana L. Popović
  • Danijela V. Todorović
  • Milan M. Zarić
  • Zoran R. Ratković
Original Research
  • 42 Downloads

Abstract

Three series of sulfonyl esters were synthesized in reactions of sulfonyl chlorides with three different phenolic chalcone analogues (dehydrozingerone (4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one), (E)-1-(4-hydroxy-3-methoxyphenyl)pent-1-en-3-one, and (E)-1-(4-hydroxy-3-methoxyphenyl)-5-methylhex-1-en-3-one). The structures of the new compounds were determined by IR, MS, and NMR methods. Screening of the new sulfonyl esters’ in vitro cytotoxic activities against human epithelial cervical carcinoma (HeLa) and normal human fibroblast (MRC-5) cell lines by the MTT method was performed. The five most active were selected and further tested on HeLa, MRC-5, and MCF-7 (breast carcinoma) cell lines. The examined compounds exhibit strong in vitro anticancer activities with moderate-to-high selectivity, inducing apoptotic cell death and cell cycle arrest in both HeLa and MCF-7 cell lines, but have little to no effect on the non-cancerous MRC-5 cell line.

Keywords

Apoptosis Chalcones Cell death Cytotoxicity Sulfonyl ester 

Notes

Acknowledgements

The authors are grateful to the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant 172034) for financial support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2283_MOESM1_ESM.docx (19 kb)
Supplementary Table S1
44_2018_2283_MOESM2_ESM.tif (1 mb)
Supplementary Figure S1

References

  1. Alcaradz LE, Blanco SE, Puig ON, Tomads F, Ferretti FH (2000) Antibacterial activity of flavonoids against methicillin-resistant Staphylococcus aureus strains. J Theor Biol 205:231–240CrossRefGoogle Scholar
  2. Anto RJ, Sukumaran K, Kuttan G, Rao MNA, Subbaraju V, Kuttan R (1995) Anticancer and antioxidant activity of synthetic chalcones and related compounds. Cancer Lett 97:33–37CrossRefGoogle Scholar
  3. Batovska D, Parushev S, Stamboliyska B, Tsvetkova I, Ninova M, Najdenski H (2009) Examination of growth inhibitory properties of synthetic chalcones for which antibacterial activity was predicted. Eur J Med Chem 44:2211–2218CrossRefGoogle Scholar
  4. Betts LM, Tam NC, Kabir SMH, Langler RF, Crandall I (2006) Ether aryl sulfonic acid esters with improved antimalarial/anticancer activities. Aust J Chem 59:277–282CrossRefGoogle Scholar
  5. Chen M, Christensen SB, Blom J, Lemmich E, Nadelmann L, Fich K, Theander TG, Kharazmi A (1993) Licochalcone A, a novel antiparasitic agent with potent activity against human pathogenic protozoan species of Leishmania. Antimicrob Agent Chemother 37:2550–2556CrossRefGoogle Scholar
  6. Chen M, Christensen SB, Theader TG, Kharazmi A (1994) Antileishmanial activity of licochalcone A in mice infected with Leishmania major and in hamsters infected with Leishmania donovani. Antimicrob Agent Chemother 38:1339–1344CrossRefGoogle Scholar
  7. Christensen ND, Reed CA, Culp TD, Hermonat PL, Howett MK, Anderson RA, Zaneveld LJ (2001) Papillomavirus microbicidal activities of high molecular weight cellulose sulphate, dextrane sulphate and polystyrene sulfonate. Antimicrob Agents Chemother 45:3427–3432CrossRefGoogle Scholar
  8. Coskun D, Erkisa M, Ulukaya E, Coskun MF, Ari F (2017) Novel 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives: synthesis, characterization and anticancer activity. Eur J Med Chem 136:212–222CrossRefGoogle Scholar
  9. Cyr L, Langler R, Lavigne C (2008) Cell cycle arrest and apoptosis responses of human breast epithelial cells to the synthetic organosulfur compound p-methoxyphenyl p-toluenesulfonate. Anticancer Res 28:2753–2764Google Scholar
  10. ElSohly HN, Joshi AS, Nimrod AC, Walker LA, Clark AM (2001) Antifungal chalcones from Maclura tinctoria. Planta Med 67:87–89CrossRefGoogle Scholar
  11. Gafner S, Wolfender JL, Mavi S, Hostettmann K (1996) Antifungal and antibacterial chalcones from Myrica serrata. Planta Med 62:67–69CrossRefGoogle Scholar
  12. Ghorab MM, Ragab FA, Heiba HI, El-Gazzar MG, Zahran SS (2015) Synthesis, anticancer and radiosensitizing evaluation of some novel sulfonamide derivatives. Eur J Med Chem 92:682–692CrossRefGoogle Scholar
  13. Hanna MA, Girges MM, Berghot MA (1991) Sulfonate ester containing (imidazol-1-yl) N-substituted benzenesulfonamides of anticipated antineoplastic activity. Phosphorus Sulfur Silicon Relat Elem 61:239–246CrossRefGoogle Scholar
  14. Hans RH, Guantai EM, Lategan C, Smith PJ, Wan B, Franzblau SG, Gut J, Rosenthal PJ, Chibale K (2010) Synthesis, antimalarial and antitubercular activity of acetylenic chalcones. Bioorg Med Chem Lett 20:942–944CrossRefGoogle Scholar
  15. Joksimović N, Baskić D, Popović S, Zarić M, Kosanić M, Ranković B, Stanojković T, Novaković SB, Davidović G, Bugarčić Z, Janković N (2016) Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper (II) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate. Dalton Trans 45:15067–15077CrossRefGoogle Scholar
  16. Kinghorn A, Farnsworth N, Soejarto D, Cordell G, Swanson S, Pezzuto J, Wani M, Wall M, Oberlies N, Kroll D, Kramer R, Rose W, Vite G, Fairchild C, Peterson R, Wild R (2003) Novel strategies for the discovery of plant derived anticancer agents. Pharm Biol 41:53–67CrossRefGoogle Scholar
  17. Lahtchev KL, Batovska DI, Parushev SP, Ubiyvovk VM, Sibirny AA (2008) Antifungal activity of chalcones: a mechanistic study using various yeast strains. Eur J Med Chem 43:2220–2228CrossRefGoogle Scholar
  18. Li R, Kenyon GL, Cohen FE, Chen X, Gong B, Dominguez JN, Davidson E, Kurzban G, Miller RE, Nuzum EO, Rosenthal PJ, McKerrow JH (1995) In vitro antimalarial activity of chalcones and their derivatives. J Med Chem 38:5031–5037CrossRefGoogle Scholar
  19. Liu M, Wilairat P, Go ML (2001) Antimalarial alkoxylated and hydroxylated chalcones: structure-activity relationship analysis. J Med Chem 44:4443–4452CrossRefGoogle Scholar
  20. Loewenthal HJE (1959) Selective reactions and modification of functional groups in steroid chemistry. Tetrahedron 6:269–303CrossRefGoogle Scholar
  21. Mahapatra DM, Bharti SK, Asati V (2015) Anti-cancer chalcones: structural and molecular target perspectives. Eur J Med Chem 98:69–114CrossRefGoogle Scholar
  22. Motohashi N, Yamagami C, Tokuda H, Konoshima T, Okuda Y, Okuda M, Mukainaka T, Nishino H, Saito Y (1998) Inhibitory effects of dehydrozingerone and related compounds on 12-O-tetradecanoylphorbol-13-acetate induced Epstein-Barr virus early antigen activation. Cancer Lett 134:37–42CrossRefGoogle Scholar
  23. Muškinja J, Ratković Z, Ranković B, Kosanić M (2016) Synthesis of o-alkyl derivatives of dehydrozingeronean alogues Kragujevac J Sci 38:97–106CrossRefGoogle Scholar
  24. Narender T, Tanvir K, Shweta N, Goyal N, Gupta S (2005) Synthesis of chromenochalcones and evaluation of their in vitro antileishmanial activity. Bioorg Med Chem 13:6543–6550CrossRefGoogle Scholar
  25. Nielsen SF, Boesen T, Larsen M, Schønning K, Kromann H (2004) Antibacterial chalcones-bioisosteric replacement of the 4′-hydroxy group. Bioorg Med Chem 12:3047–3054CrossRefGoogle Scholar
  26. Nielsen SF, Chen M, Theander TG, Kharazmi A, Christensen SB (1995) Synthesis of antiparasitic licorice chalcones. Bioorg Med Chem Lett 5:449–452CrossRefGoogle Scholar
  27. Nielsen SF, Kharazmi A, Christensen SB (1998) Modifications of the alpha,beta-double bond in chalcones only marginally affect the antiprotozoal activities. Bioorg Med Chem 6:937–945CrossRefGoogle Scholar
  28. Park JY, Jeong HJ, Kim YM, Park SJ, Rho MC, Park KH, Ryu YB, Lee WS (2011) Characteristic of alkylated chalcones from Angelica keiskei on influenza virus neuraminidase inhibition. Bioorg Med Chem Lett 21:5602–5604CrossRefGoogle Scholar
  29. Phrutivorapongkul A, Lipipun V, Ruangrungsi N, Kirtikara K, Nishikawa K, Maruyama S, Watanabe T, Ishikawa T (2003) Studies on the chemical constituents of stem bark of Millettia leucantha: Isolation of new chalcones with cytotoxic, anti-herpes simplex virus and anti-inflammatory activities. Chem Pharm Bull 51:187–190CrossRefGoogle Scholar
  30. Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G (2016) Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging 8:603–619CrossRefGoogle Scholar
  31. Rajasekar S, Park DJ, Park C, Park S, Park YH, Kim ST, Choi YH, Choi YW (2012) In vitro and in vivo anticancer effects of Lithospermum erythrorhizon extract on B16F10 murine melanoma. J Ethnopharmacol 144:335–345CrossRefGoogle Scholar
  32. Rusconi S, Moonis M, Merrill DP, Pallai PV, Neidhardt EA, Singh SK, Osburne MS, Profy AT, Jenson JC, Hirsch MS (1996) Naphthalene sulfonate polymers with CD-4 blocking and antihuman immunodeficiency virus type 1 activities. Antimicrob Agents Chemother 40:234–236CrossRefGoogle Scholar
  33. Shapiro GI, Harper JW (1999) Anticancer drug targets: cell cycle and checkpoint control. J Clin Invest 15:1645–1653CrossRefGoogle Scholar
  34. Sivakumar PM, Geetha Babu SM, Mukesh D (2007) QSAR studies on chalcones and flavonoids as anti-tuberculosis agents using genetic function approximation (GFA) method. Chem Pharm Bull 55:44–49CrossRefGoogle Scholar
  35. Sivakumar PM, Prabhakar PK, Doble M (2011) Synthesis, antioxidant evaluation, and quantitative structure-activity relationship studies of chalcones. Med Chem Res 20:482–492CrossRefGoogle Scholar
  36. Smith LR (1996) Rheosmin (“raspberry ketone”) and zingerone, and their preparation by crossed aldol-catalytic hydrogenation sequences. Chem Educ 1:1–18Google Scholar
  37. Trivedi JC, Bariwal JB, Upadhyay KD, Naliapara YT, Joshi SK, Pannecouque CC, Clercq ED, Shah AK (2007) Improved and rapid synthesis of new coumarinyl chalcone derivatives and their antiviral activity. Tetrahedron Lett 48:8472–8474CrossRefGoogle Scholar
  38. Tseng CH, Tzeng CC, Hsu CY, Cheng CM, Yang CN, Chen YL (2015) Discovery of 3-phenylquinolinyl chalcone derivatives as potent and selective anticancer agents against breast cancers. Eur J Med Chem 97:306–319CrossRefGoogle Scholar
  39. Vasil’ev RF, Kancheva VD, Fedorova GF, Batovska DI, Trofimov AV (2010) Antioxidant activity of chalcones: the chemiluminescence determination of the reactivity and the quantum chemical calculation of the energies and structures of reagents and intermediates. Kinet Catal 51:507–515CrossRefGoogle Scholar
  40. Vogel S, Ohmayer S, Brunner G, Heilmann J (2008) Natural and non-natural prenylated chalcones: synthesis, cytotoxicity and anti-oxidative activity. Bioorg Med Chem 16:4286–4293CrossRefGoogle Scholar
  41. Yadav HL, Gupta P, Pawar PS, Singour PK, Patil UK (2010) Synthesis and biological evaluation of anti-inflammatory activity of 1,3-diphenyl propenone derivatives. Med Chem Res 19:1–8Google Scholar
  42. Zaric M, Mitrovic M, Nikolic I, Baskic D, Popovic S, Djurdjevic P, Milosavljevic Z, Zelen I (2015) Chrysin induces apoptosis in peripheral blood lymphocytes isolated from human chronic lymphocytic leukemia. Anti-Cancer Agents Med Chem 15:189–195CrossRefGoogle Scholar
  43. Zhang XW, Zhao DH, Quan YC, Sun LP, Yin XM, Guan LP (2010) Synthesis and evaluation of anti-inflammatory activity of substituted chalcone derivatives. Med Chem Res 19:403–412CrossRefGoogle Scholar
  44. Zsoldos-Mady V, Csampai A, Szabo R, Meszaros-Alapi E, Pasztor J, Hudecz F, Sohar P (2006) Synthesis, structure, and in vitro antitumor activity of some glycoside derivatives of ferrocenyl‐chalcones and ferrocenyl‐pyrazolines. Chem Med Chem 1:1119–1125CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Jovana M. Muškinja
    • 1
  • Adrijana Z. Burmudžija
    • 1
  • Dejan D. Baskić
    • 2
    • 3
  • Suzana L. Popović
    • 3
  • Danijela V. Todorović
    • 4
  • Milan M. Zarić
    • 5
  • Zoran R. Ratković
    • 1
  1. 1.Department of ChemistryFaculty of Science, University of KragujevacKragujevacSerbia
  2. 2.Public Health Institute KragujevacKragujevacSerbia
  3. 3.Department of Microbiology and ImmunologyFaculty of Medical Sciences, University of Kragujevac, Center for Molecular Medicine and Stem Cell ResearchKragujevacSerbia
  4. 4.Department of GeneticsFaculty of Medical Sciences, University of KragujevacKragujevacSerbia
  5. 5.Department of BiochemistryFaculty of Medical Sciences, University of KragujevacKragujevacSerbia

Personalised recommendations