Advertisement

Synthesis, structural characterization, and cytotoxic evaluation of chalcone derivatives

  • Paulo N. Bandeira
  • Telma L. G. Lemos
  • Hélcio S. Santos
  • Mylena C. S. de Carvalho
  • Daniel P. Pinheiro
  • Manoel O. de Moraes Filho
  • Cláudia Pessoa
  • Francisco W. A. Barros-Nepomuceno
  • Tigressa H. S. Rodrigues
  • Paulo R. V. Ribeiro
  • Herbert S. Magalhães
  • Alexandre M. R. TeixeiraEmail author
Original Research
  • 33 Downloads

Abstract

Chalcones containing amino or acetamide groups on ring A and electron donating/withdrawing groups on ring B have been shown to have great cytotoxic potential against human cancer cell lines. In this work, a series of twenty chalcones, including nine 1-(4′-aminophenyl)-3-(substituted aryl)-2-propen-1-ones (19), nine 1-(4′-acetamidophenyl)-3-(substituted aryl)-2-propen-1-ones (1a9a), and two 1-(3′-methoxy-4′-hydroxyphenyl)-3-(substituted aryl)-2-propen-1-ones (10, 11), were synthesized and submitted for initial biological screening using HCT-116 cells. Among the evaluated compounds, chalcone 6a showed strong and selective activity against HCT-116 cells (IC50 = 2.37 ± 0.73 µM). The preliminary structure–activity relationship analysis indicated that the cytotoxic effect of these compounds might be attributed to the combined effect of two electron withdrawing groups: the nitro group (NO2) at the meta-position of ring B and the acetyl group at the para-position of ring A. Moreover, chalcone 6a was able to induce G2/M cell cycle arrest and apoptosis at a concentration of 10 µM after 24 h of incubation. These data reinforce that compound 6a could be a promising lead compound for the future exploration of selective anti-colon carcinoma cancer agents.

Keywords

Synthesis NMR Infrared Chalcone 4′-acetamidochalcones Cytotoxic activity 

Notes

Acknowledgements

The authors thank the National Cancer Institute (Bethesda, MD, USA) for donating of all human tumor cell lines used in this study. CENAUREMN—Northeastern Center for the Application and Use of Nuclear Magnetic Resonance and EMBRAPA AGROINDÚSTRIA TROPICAL-Multiuser Laboratory of Natural Product Chemistry by obtaining the spectral data. Teixeira AMR also acknowledges financial support from the PQ/CNPq (Grant#: 3 05719/2018-1).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

44_2019_2434_MOESM1_ESM.docx (18.5 mb)
Supplementary Information

References

  1. Abbas A, Naseer MM, Hasan A, Hadda TB (2014) Synthesis and cytotoxicity studies of 4-Alkoxychalcones as new antitumor agents. J Mater Environ Sci 5:281–292Google Scholar
  2. Bhat BA, Dhar KL, Puri SC, Saxena AK, Shanmugavel M, Qazi GN (2005) Synthesis and biological evaluation of chalcones and their derived pyrazoles as potential cytotoxic agents. Bioorg Med Chem Lett 15:3177–3180CrossRefGoogle Scholar
  3. Boeck P, Bandeira Falcão CA, Leal PC, Yunes RA, Filho VC, Torres-Santos EC, Rossi-Bergmann B (2006) Synthesis of chalcone analogues with increased antileishmanial activity. Bioorg Med Chem 14:1538–1545CrossRefGoogle Scholar
  4. Bond MJ, Bleiler M, Harrison LE, Scocchera EW, Nakanishi M, G-Dayanan N, Keshipeddy S, Rosenberg DW, Wright DL, Giardina C (2018) Spindle assembly disruption and cancer cell apoptosis with a CLTC-binding compound. Mol Cancer Res 16:1361–1372CrossRefGoogle Scholar
  5. Cabrera M, Simoens M, Falchi G, Lavaggi ML, Piro OE, Castellano EE, Vidal A, Azqueta A, Monge A, de Ceráin AL, Sagrera G, Seoane G, Cerecetto H, González M (2007) Synthetic chalcones, flavanones, and flavones as antitumoral agents: biological evaluation and structure–activity relationships. Bioorg Med Chem 15:3356–3367CrossRefGoogle Scholar
  6. Corrêa R, Pereira MAS, Buffon D, dos Santos L, Filho VC, Santos ARS, Nunes RJ(2001) Antinociceptive properties of chalcones. Structure-activity relationships. Arch Pharm 334:332–334CrossRefGoogle Scholar
  7. De Campos-Buzzi F, Padaratz P, Meira VA, Corrêa R, Nunes JR, Cechinel-Filho V (2007) 4′-acetamidochalcone derivatives as potential antinociceptive agents. Molecules 12:896–906CrossRefGoogle Scholar
  8. de Campos-Buzzi F, Pereira de Campos J, Pozza Tonini P, Corrêa R, Augusto Yunes R, Boeck P, Cechinel-Filho V (2006) Antinociceptive effects of synthetic chalcones obtained from xanthoxyline. Arch Pharm 339:361–365CrossRefGoogle Scholar
  9. Das M, Manna K (2016) Chalcone scaffold in anticancer armamentarium: a molecular insight. J Toxicol 6:7651047Google Scholar
  10. Di Carlo G, Mascolo N, Izzo AA, Capasso F (1999) Flavonoids: old and new aspects of a class of natural therapeutic drugs. Life Sci 65:337–353CrossRefGoogle Scholar
  11. Ducki S, Forrest R, Hadfield JA, Kendall A, Lawrence NJ, McGown AT, Rennison D (1998) Potent antimitotic and cell growth inhibitory properties of substituted chalcones. Bioorg Med Chem Lett 8:1051–1056CrossRefGoogle Scholar
  12. Guilherme AM, Jardim T, Guimaraes T, Maria do Carmo FR, Pinto BC, Cavalcanti KMF, Pessoa C, Gatto CC, Nair DK, Namboothiri INN, Junior ENS (2015) Naphthoquinone-based chalcone hybrids and derivatives: synthesis and potent activity against cancer cell lines. Med Chem Comm 6:120–130CrossRefGoogle Scholar
  13. Guo L, Zhang H, Tian M, Tian Z, Xu Y, Yang Y, Peng H, Liu P, Liu Z (2018) Electronic effects on reactivity and anticancer activity by half-sandwich N,N-chelated iridium (III) complexes. New J Chem 42:1–22CrossRefGoogle Scholar
  14. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRefGoogle Scholar
  15. Hassan GS, El-Messery SM, Abbas A (2017) Synthesis and anticancer activity of new thiazolo[3,2-a]pyrimidines: DNA binding and molecular modeling study. Bioorg Chem 74:41–52CrossRefGoogle Scholar
  16. Jardim GAM, Guimarães TT, Pinto MCFR, Cavalcanti BC, Farias KM, Pessoa C, Gatto CC, Nair DK, Namboothir INN, Júnior ENS (2015) Naphthoquinone-based chalcone hubrids and derivatives: synthesis and potent activity against cancer cell lines. Med Chem Comm 6:120–130CrossRefGoogle Scholar
  17. Karaman İ, Gezegen H, Gürdere MB, Dingil A, Ceylan M (2010) Screening of biological activities of a series of chalcone derivatives against human pathogenic microorganisms. Chem Biodivers 7:400–408CrossRefGoogle Scholar
  18. Karthikeyan CN, Moorthy SH, Ramasamy N, Vanam S, Manivannan U, Karunagaran ED, Trivedi P (2015) Advances in chalcones with anticancer activities. Recent Pat Anticancer Drug Discov 10:97–115CrossRefGoogle Scholar
  19. Kepp O, Galluzzi L, Lipinski M, Yuan J, Kroemer G (2011) Cell death assays for drug discovery. Nat Rev Drug Discov 10:221–237CrossRefGoogle Scholar
  20. Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nuñez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G (2008) Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ 16:3–11CrossRefGoogle Scholar
  21. Lindamulage IK, Vu H-Y, Karthikeyan C, Knockleby J, Lee Y-F, Trivedi P, Lee H (2017) Novel quinolone chalcones targeting colchicine-binding pocket kill multidrug-resistant cancer cells by inhibiting tubulin activity and MRP1 function. Sci Rep 7:1–5CrossRefGoogle Scholar
  22. Martel-Frachet V, Keramidas M, Nurisso A, DeBonis S, Rome C, Coll JL, Ahcène B, Skoufias DA, Ronot X (2015) IPP51, a chalcone acting as a microtubule inhibitor with in vivo antitumor activity against bladder carcinoma. Oncotarget 6:14669–14686CrossRefGoogle Scholar
  23. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63CrossRefGoogle Scholar
  24. Nazir S, Ansari FL, Hussain T, Mazhar K, Muazzam AG, Qasmi ZU, Makhmoor T, Noureen H, Mirza B (2013) Brine shrimp lethality assay ‘an effective prescreen’: microwave-assisted synthesis, BSL toxicity and 3DQSAR studies-based designing, docking and antitumor evaluation of potent chalcones. Pharm Biol 51:1091–1093CrossRefGoogle Scholar
  25. Nowakowska Z (2007) A review of anti-infective and anti-inflammatory chalcones. Eur J Med Chem 42:125–137CrossRefGoogle Scholar
  26. Padaratz P, Fracasso M, De Campos-Buzzi F, Corrêa R, Niero R, Monache FD, Cechinel-Filho V (2009) Antinociceptive activity of a new benzofuranone derived from a chalcone. Basic Clin Pharm Toxicol 105:257–261CrossRefGoogle Scholar
  27. Pereira UA, Moreira TA, Barbosa LCA, Maltha CRA, Bomfim IS, Maranhão SS, Moraes MO, Pessoa C, Barros-Nepomuceno FWA (2016) Rubrolide analogues and their derived lactams as potential anticancer agents. Med Chem Comm 7:345–352CrossRefGoogle Scholar
  28. Prasad YR, Rani VJ, Rao AS (2013) In vitro antioxidant activity and scavenging effects of some synthesized 4’-aminochalcones. Asian J Chem 25:52–58CrossRefGoogle Scholar
  29. Rossette MC, Moraes DC, Sacramento EK, Romano-Silva MA, Carvalho JL, Gomes DA, Caldas H, Friedman E, Bastos-Rodrigues L, De Marco L (2017) The in vitro and in vivo antiangiogenic effects of Flavokawain B. Phytother Res 31:1607–1613CrossRefGoogle Scholar
  30. Santos MB, Pinhanelli VC, Garcia MAR, Silva G, Baek SJ, França SC, Fachim AL, Marins M, Regasini LO (2017) Antiproliferative and pro-apoptotic activities of 2- and 4-aminochalcones against tumor canine cells. Eur J Med Chem 138:884–889CrossRefGoogle Scholar
  31. Shankaraiah N, Nekkanti S, Brahma UR, Praveen Kumar N, Deshpande N, Prasanna D, Senwar KR, Jaya Lakshmi U (2017) Synthesis of different heterocycles-linked chalcone conjugates as cytotoxic agents and tubulin polymerization inhibitors. Bioorg Med Chem 25:4805–4816CrossRefGoogle Scholar
  32. Zingales SK, Moore ME (2016) Design and Synthesis of (2-(furanyl)vinyl)-1-tetralone chalcones as anticancer agents. Der Pharma Chem 8:40–47Google Scholar
  33. Tristão TC, Campos-Buzzi F, Cruz RCB, Filho VC, Cruz AB (2012) Antimicrobial and citotoxicity potential of acetamido, amino and nitrochalcones. Arzneimittelforschung 62:590–594CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Paulo N. Bandeira
    • 1
  • Telma L. G. Lemos
    • 2
  • Hélcio S. Santos
    • 1
    • 3
  • Mylena C. S. de Carvalho
    • 4
  • Daniel P. Pinheiro
    • 4
  • Manoel O. de Moraes Filho
    • 4
  • Cláudia Pessoa
    • 4
    • 5
  • Francisco W. A. Barros-Nepomuceno
    • 6
  • Tigressa H. S. Rodrigues
    • 1
  • Paulo R. V. Ribeiro
    • 7
  • Herbert S. Magalhães
    • 2
  • Alexandre M. R. Teixeira
    • 3
    Email author
  1. 1.Curso de QuímicaUniversidade Estadual Vale do AcaraúSobralBrazil
  2. 2.Departamento de Química Orgânica e InorgânicaUniversidade Federal do CearáFortalezaBrazil
  3. 3.Departamento de Química BiológicaUniversidade Regional do CaririCratoBrazil
  4. 4.Núcleo de Pesquisa e Desenvolvimento de MedicamentosUniversidade Federal do CearáFortalezaBrazil
  5. 5.Fundação Oswaldo Cruz, FIOCRUZ-CEEusebioBrazil
  6. 6.Instituto de Ciências da SaúdeUniversidade da Integração Internacional da Lusofonia Afro-BrasileiraAcarapeBrazil
  7. 7.Laboratório Multiusuário de Química de Produtos NaturaisEmbrapa Agroindústria TropicalFortalezaBrazil

Personalised recommendations