Skip to main content
SpringerLink
Log in

Synthesis and in vitro cytotoxic evaluation of new triazole derivatives based on artemisinin via click chemistry

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

The paper presents the synthesis of new artemisinin triazole derivatives via click chemistry and their in vitro cytotoxic evaluation against four cancer cell lines including MCF-7, LU-1, HL-60 and P388. The bioassay result showed that most of the target compounds were active against four cell lines, in which compounds 11g displayed the most potent inhibitory activity against HL-60 cell line with IC50 value of 2.5 μM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Scheme 2
Scheme 3
Fig. 2

Similar content being viewed by others

References

  • Aminake MN, Mahajan A, Kumar V, Hans R, Wiesner L, Taylor D, Kock C, Grobler A, Smith PJ, Kirschner M, Rethwilm A, Pradel G, Chibale K (2012) Synthesis and evaluation of hybrid drugs for a potential HIV/AIDS-malaria combination therapy. Bioorg Med Chem 20(17):5277–5289

    Article  CAS  PubMed  Google Scholar 

  • Blazqueza AG, Dolon MF, Vicente LS, Maestre AD, Miguel ABG, Alvarez M, Serrano MA, Jansen H, Efferth T, Marin JJG, Romero MR (2013) Novel artemisinin derivatives with potential usefulness against liver/colon cancer and viral hepatitis. Bioorg Med Chem 21(14):4432–4444

    Article  Google Scholar 

  • Chaturvedi D, Goswami A, Saikia PP, Barua NC, Rao PG (2010) Artemisinin and its derivatives: a novel class of anti-malarial and anti-cancer agents. Chem Soc Rev 39(2):435–454

    Article  CAS  PubMed  Google Scholar 

  • Chhikara BS, Jean NS, Mandal D, Kumar A, Parang K (2011) Fatty acyl amide derivatives of doxorubicin: synthesis and in vitro anticancer activities. Eur J Med Chem 46(6):2037–2042

    Article  CAS  PubMed  Google Scholar 

  • Cho S, Oh S, Um Y, Jung JH, Ham J, Shin W, Lee S (2009) Synthesis of 10-substituted triazolyl artemisinins possessing anticancer activity via Huisgen 1,3-dipolar cylcoaddition. Bioorg Med Chem Lett 19(2):382–385

    Article  CAS  PubMed  Google Scholar 

  • Goswami A, Saikia PP, Saikia B, Barua NC, Saxena AK, Suri N, Sharma M, Baishya G (2013) Synthesis of a novel series of highly functionalized Baylis–Hillman adducts of artemisinin with potent anticancer activity. Tetrahedron Lett 54(32):4221–4224

    Article  CAS  Google Scholar 

  • Huanan H, Zhang A, Ding L, Lei X, Zhang L (2008) Regioselective synthesis of 1-(2,6-dichloro-4-trifluoromethylphenyl)-4-alkyl-1H-[1,2,3]-triazoles. Molecules 13:556–566

    Article  Google Scholar 

  • Jung M, Park N, Moon H-I, Lee Y, Chung W-Y, Park K-K (2009) Synthesis and anticancer activity of novel amide derivatives of non-acetal deoxoartemisinin. Bioorg Med Chem Lett 19(22):6303–6306

    Article  CAS  PubMed  Google Scholar 

  • Karolyi BI, Bosze S, Orban E, Sohar P, Drahos L, Gal E, Csampai A (2012) Acylated mono, bis- and tris-cinchona-based amines containing ferrocene or organic residues: synthesis, structure and in vitro antitumor activity on selected human cancer cell lines. Molecules 17:2316–2329

    Article  CAS  PubMed  Google Scholar 

  • Klayman DL (1985) Qinghaosu (artemisinin): an antimalarial drug from China. Science 228(4703):1049–1055

    Article  CAS  PubMed  Google Scholar 

  • Klaymann DL (1993) In: ACS Symposium Series, vol 534, pp 242–255

  • Kolb HC, Sharpless KB (2003a) The growing impact of click chemistry on drug discovery. Res Focus 8(24):1128–1137

    CAS  Google Scholar 

  • Kolb HC, Sharpless KB (2003b) The growing impact of click chemistry on drug discovery. Drug Discov Today 8(24):1128–1137

    Article  CAS  PubMed  Google Scholar 

  • Lee S (2011) Synthesis of 10β-substituted triazolyl artemisinins and their growth inhibitory activity against various cancer cells. Bull Korean Chem Soc 32(2):737–740

    Article  CAS  Google Scholar 

  • Lee BY, Park SR, Jeon HB, Kim KS (2006) A new solvent system for efficient synthesis of 1,2,3-triazoles. Tetrahedron Lett 47(29):5105–5109

    Article  CAS  Google Scholar 

  • Lewis WG, Green LG, Grynszpan F, Radic Z, Carlier PR, Taylor P, Finn GM, Sharpless KB (2002) Click Chemistry in situ: acetylcholinesterase as a reaction vessel for the selective assembly of a femtomolar inhibitor from an array of building blocks. Angew Chem Int Ed 114(6):1095–1099

    Article  Google Scholar 

  • Li Y, Shan F, Wu JM, Wu GS, Ding J, Xiao D, Yang WY, Atassi G, Le’once S, Caignard DH, Renard P (2001) Novel antitumor artemisinin derivatives targeting G1 phase of the cell cycle. Bioorg Med Chem Lett 11(1):5–8

    Article  PubMed  Google Scholar 

  • Li Y, Wu JM, Shan F, Wu GS, Ding J, Xiao D, Han JX, Atassi G, Leonce S, Caignard DH, Renard P (2003) Synthesis and cytotoxicity of dihydroartemisinin ethers containing cyanoarylmethyl group. Bioorg Med Chem 11(6):977–984

    Article  CAS  PubMed  Google Scholar 

  • Mercer AEM, James L, Xiao-Ming S, Cohen GM, Chadwick J, O’Neill PM, Park BK (2007) Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds. J Biol Chem 282:9372–9382

    Article  CAS  PubMed  Google Scholar 

  • Mercer AE, Copple IM, Maggs JL, O’Neill PM, Park BK (2011) The role of heme and the mitochondrion in the chemical and molecular mechanisms of mammalian cell death induced by the artemisinin antimalarials. J Biol Chem 286:987–996

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Monks A, Scudiero D, Skehan P, Shoemake R, Paull K, Vistica D, Hose C, Langley J, Cronise P, Campbell H, Mayo J, Boyd M (1991) Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst 83(11):757–766

    Article  CAS  PubMed  Google Scholar 

  • Oh S, Shin WS, Ham J, Lee S (2010) Acid-catalyzed synthesis of 10-substituted triazolyl artemisinins and their growth inhibitory activity against various cancer cells. Bioorg Med Chem Lett 20(14):4112–4115

    Article  CAS  PubMed  Google Scholar 

  • Oh S, Shin WS, Ham J, Lee S (2011) Synthesis of artemisinin with substituted sulfidyl or sulfonyl moiety and their anti-angiogenesis activity. Bull Korean Chem Soc 32(8):2823–2826

    Article  Google Scholar 

  • Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) Stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed 114(14):2704–2711

    Article  Google Scholar 

  • Scudiero DA, Shoemaker RH, Paull KD, Monks A, Tierney S, Nofziger TH, Currens MJ, Seniff D, Boyd MR (1988) Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res 48:4827–4833

    CAS  PubMed  Google Scholar 

  • Singh NP, Lai H (2001) Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sci 70(1):49–56

    Article  CAS  PubMed  Google Scholar 

  • Singh NP, Lai HC (2004) Artemisinin induces apoptosis in human cancer cells. Anticancer Res 24(4):2277–2280

    CAS  PubMed  Google Scholar 

  • Slade D, Galal AM, Gul W, Radwan MM, Ahmed SA, Khan SI, Tekwani BL, Jacob MR, Ross SA, ElSohly MA (2009) Antiprotozoal, anticancer and antimicrobial activities of dihydroartemisinin acetal dimers and monomers. Bioorg Med Chem 17(23):7949–7957

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Souza MV, Pais KC, Kaiser CR, Peralta MA, Ferreiraa ML, Lourenço MCS (2009) Synthesis and in vitro antitubercular activity of a series of quinoline derivatives. Bioorg Med Chem 17(4):1474–1480

    Article  PubMed  Google Scholar 

  • Tron GC, Pirali T, Billington RA, Canonico PL, Sorba G, Genazzani AA (2008) Click chemistry reactions in medicinal chemistry: applications of the 1,3-dipolar cycloaddition between azides and alkynes. Med Res Rev 28(2):278–308

    Article  CAS  PubMed  Google Scholar 

  • Xie L, Zhai X, Ren L, Meng H, Liu C, Wufu Zhu W, Zhao Y (2011) Design, synthesis and antitumor activity of novel artemisinin derivatives using hybrid approach. Chem Pharm Bull 59(8):984–990

    Article  CAS  PubMed  Google Scholar 

  • Yang ZS, Zhou WL, Sui Y, Wang JX, Wu JM, Zhou Y, Zhang YP, He L, Han JY, Tang W, Zuo JP, Li Y (2005) Synthesis and immunosuppressive activity of new artemisinin derivatives. 1. [12(beta or alpha)-Dihydroartemisininoxy]phen(ox)yl aliphatic acids and esters. J Med Chem 48(14):4608–4617

    Article  CAS  PubMed  Google Scholar 

  • Yang ZS, Wang JX, Zhou Y, Zuo JP, Li Y (2006) Synthesis and immunosuppressive activity of new artemisinin derivatives. Part 2: 2-[12(beta or alpha)-dihydroartemisinoxymethyl(or 1′-ethyl)]phenoxyl propionic acids and esters. Bioorg Med Chem 14(23):8043–8049

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Solomon VR, Hu C, Ulibarri G, Lee H (2008) Synthesis and in vitro cytotoxicity evaluation of 4-aminoquinoline derivatives. Biomed Pharmacother 62(2):65–69

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Vietnam National Foundation for Science and Technology Development (NAFOSTED) for financial support via a Project 104.01.2013.01.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry and Pesticides Technology, School of Chemical Engineering, Hanoi University of Science and Technology, No. 1 Dai Co Viet Street, Hai Ba Trung District, Hanoi, Vietnam

    Le Huy Binh, Nguyen Thi Thuy Van, Vu Tuan Kien, Nguyen Thi Thuy My, Hoang Xuan Tien & Tran Khac Vu

  2. Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Caugiay, Hanoi, Vietnam

    Luu Van Chinh & Nguyen Thi Nga

  3. Laboratory for Bioassay, Institute of Biotechnology, Vietnam Academy of Science and Technology, 18-Hoang Quoc Viet, Caugiay, Hanoi, Vietnam

    Do Thi Thao

Authors
  1. Le Huy Binh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nguyen Thi Thuy Van
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vu Tuan Kien
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nguyen Thi Thuy My
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luu Van Chinh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nguyen Thi Nga
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hoang Xuan Tien
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Do Thi Thao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tran Khac Vu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tran Khac Vu.

Ethics declarations

Conflict of interest

The authors have reported no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Binh, L.H., Van, N.T.T., Kien, V.T. et al. Synthesis and in vitro cytotoxic evaluation of new triazole derivatives based on artemisinin via click chemistry. Med Chem Res 25, 738–750 (2016). https://doi.org/10.1007/s00044-016-1524-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-016-1524-z

Keywords

Search

Navigation