Skip to main content

Advertisement

SpringerLink
Log in

Design, synthesis and biological evaluation of novel furoxan-based coumarin derivatives as antitumor agents

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

Abstract

In order to find new anticancer drugs, a series of novel furoxan-based coumarin derivatives (10a–k) were synthesized and evaluated for their antiproliferative activities in vitro. All compounds displayed more potent inhibition on human cervical cancer HeLa cell proliferation than coumarin-3-carboxylic acid, and compounds 10b, 10c, 10f, 10h, and 10i with IC50 values ranging from 0.88 to 5.95 μM were even stronger than doxorubicin (IC50 = 10.21 μM). The further study showed that compound 10i exerted the highest antiproliferative activity (IC50 = 0.60 μM) against human breast cancer MCF-7 cells, and compound 10f had broader spectrum antiproliferative activity against five cancer cells with IC50 values in the low micromolar range of 1.86–9.85 μM. More interestingly, compound 10f had little effect on normal intestinal epithelial CCD841 cells. Our findings suggest that these novel furoxan-based coumarin derivatives may provide a new framework for the discovery of novel antitumor agents for the intervention of human carcinoma cells.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Scheme 1
Fig. 4

Similar content being viewed by others

References

  • Adams M, Ettl S, Kunert O, Wube AA, Haslinger E, Bucar F, Bauer R (2006) Antimycobacterial activity of geranylated furocoumarins from tetradium daniellii. Planta Med 72:1132–1135

    Article  CAS  PubMed  Google Scholar 

  • Appendino G, Bianchi F, Bader A, Campagnuolo C, Fattorusso E, Scafati O, Molina M, Macho A, Fiebich B, Bremner P, Heinrich M, Ballero M, Muñoz E (2004) Coumarins from opopanax chironium. New dihydrofurancoumarins and differential induction of apoptosis by imperatorin and heraclenin. J Nat Prod 67:532–536

    Article  CAS  PubMed  Google Scholar 

  • Boiani M, Cerecetto H, Gonzalez M, Risso M, Olea-Azar C, Piro OE, Castella EE, de Cerain AL, Ezpeleta O, Monge -Vega A (2001) 1,2,5-Oxadiazole N-oxide derivatives as potential anti-cancer agents: synthesis and biological evaluation. Part IV. Eur J Med Chem 36:771–782

    Article  CAS  PubMed  Google Scholar 

  • Cardellina JH, Bokesch HR, McKee TC, Boyd MR (1995) Resolution and comparative anti-HIV evaluation of the enantiomers of calanolides A and B. Bioorg Med Chem Lett 4:1011–1014

    Article  Google Scholar 

  • Cerecetto H, Porcal W (2005) Pharmacological properties of furoxans and benzofuroxans: recent developments. Mini-Rev Med Chem 5:57–71

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Wang HD, Xia X, Kung HF, Pan Y, Kong LD (2007) Behavioral and biochemical studies of total furo-coumarins from seeds of Psoralea corylifolia in the chronic mild stress model of depression in mice. Phytomedicine 14:523–529

    Article  CAS  PubMed  Google Scholar 

  • Cui HH, Gao YH, Liang SL, Cai HF, Wei ZX (2007) Chemical constituents of Citrus medica var. sarcodactylis from Sichuan Province (I). Chin Tradit Herb Drugs 9:1304–1306

    Google Scholar 

  • Gao LL, Huang JK, He LQ (2014) Design, synthesis, and evaluation of coumarin-3-carboxylic acid nicotinic acid prodrugs as novel platelet aggregation inhibitors. Chem World 7:430

    Google Scholar 

  • He LQ, Liu J, Yin DK, Zhang YH, Wang XS (2010) Synthesis and biological evaluation of nitric oxide-releasing matrine derivatives as anticancer agents. Chin Chem Lett 21:381–384

    Article  CAS  Google Scholar 

  • He LQ, Yang Q, Wu YX, Wang XS (2015) Novel hybrids of (phenylsulfonyl)furoxan and N-benzyl matrinol as anti-hepatocellular carcinoma agents. Acta Pharm Sin 50:574–578

    CAS  Google Scholar 

  • Hofseth LJ, Hussain SP, Wogan GN, Harris CC (2003) Nitric oxide in cancer and chemoprevention. Free Radic Biol Med 34:955–968

    Article  CAS  PubMed  Google Scholar 

  • Hsieh MJ, Chen MK, Yu YY (2014) Psoralen reverses docetaxel-induced multidrug resistance in A549/D16 human lung cancer cells lines. Phytomedicine 49:970–977

    Article  Google Scholar 

  • Huang Z, Fu J, Zhang Y (2017) Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects Journal of Medicinal Chemistry 60(18):7617–7635

    Article  CAS  PubMed  Google Scholar 

  • Kamath PR, Sunil D, Ajees AA (2015) Some new indole–coumarin hybrids; synthesis, anticancer and Bcl-2 docking studies. Bioorg Chem 63:101–109

    Article  CAS  PubMed  Google Scholar 

  • Liu MM, Chen XY, Huang YQ, Feng P, Guo YL, Yang G, Chen Y (2014) Hybrids of phenylsulfonylfuroxan and coumarin as potent antitumor agents. J Med Chem 57:9343–9356

    Article  CAS  PubMed  Google Scholar 

  • Mo ZL, Liu YZ, Chen H, Sun WH, Li HJ (2006) Study on the fluorescence of poly(amidoamine) dendrimers decorated with coumarin-3-methyl acyl chloride on the periphery. Spectrosc Spectr 11:2080–2084

    Google Scholar 

  • Newman DJ, Cragg GM (2016) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 79:629–661

    Article  CAS  PubMed  Google Scholar 

  • Piao XL, Yoo HH, Kim HY, Kang TL, Hwang GS, Park JH (2004) Antioxidative activity of furanocoumarins isolated from angelicae dahuricae. J Ethnopharmacol 93:243–246

    Article  CAS  PubMed  Google Scholar 

  • Vilar S, Quezada E, Santana L, Uriarte E, Yánez M, Fraiz N, Alcaide C, Canob E, Orallob F (2006) Design, synthesis, and vasorelaxant and platelet anti-aggregatory activities of coumarin–resveratrol hybrids. Bioorg Med Chem Lett 16:257–261

    Article  CAS  PubMed  Google Scholar 

  • Wang JX, Zhang BH, Xu DD (2013) Synthesis and antitumor activity of NO-donating derivatives of gambogic acid. Chin J Nat Med 11:87–96

    Article  Google Scholar 

  • Wang L, Wu HL, Yin XL, Hu Y, Gu HW, Yu RQ (2017) Simultaneous determination of umbelliferone and scopoletin in Tibetan medicine Saussurea laniceps and traditional Chinese medicine Radix angelicae pubescentis using excitation-emission matrix fluorescence coupled with second-order calibration method. Spectrochim Acta A 170:104–110

    Article  CAS  Google Scholar 

  • Wink DA, Vodovotz Y, Cook JA, Krishna MC, Kim S, Coffin D, DeGraff W, Deluca AM, Liebmann J, Mitchell JB (1998) The role of nitric oxide chemistry in cancer treatment. Biochemistry 63:802–803

    CAS  PubMed  Google Scholar 

  • Wu SH, Zhang ZH, Zhao JB (1998) An experimental study on antitumor activity of psoralen on mammary cancer cell line EMT6 in vitro and in vivo. Chin J Chin Mater Med 23:303–305

    CAS  Google Scholar 

  • Wu YX, Huang JK, Gao LL, He LQ, Huang P, Wang XS (2015) Design, synthesis and evaluation of nitric oxide-releasing derivatives of N-(n-butyl)matrinic acid and N-(n-butyl)matrinol as anti-hepatocellular carcinoma agents. Heterocycles 91:301–312

    Article  CAS  Google Scholar 

  • Zhou HY, Hong JL, Shu P, Ni YJ, Qin MJ (2009) A new dicoumarin and anticoagulant activity from Viola yedoensis Makino. Fitoterapia 80:283–285

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the financial support by the Nature and Science Foundation of Department of Education, Anhui province in China (No. KJ2016B03; No.KJ2014A134), Jiangsu Province Postdoctoral Science Foundation (1601136B), and the National Natural Science Foundation of China (No. 8127400).

Author information

Author notes

    Authors and Affiliations

    1. Anhui University of Chinese Medicine, 230012, Anhui, China

      Zhuo Zhang, Zhi-Wei Bai, Li-Qin He, Peng Huang & Rong-Feng Hu

    2. School of Pharmacy, Nantong University, 226001, Nantong, China

      Yong Ling

    3. West Anhui Health Vocational College, 237005, Anhui, China

      Hong-Xia Gu

    Authors
    1. Zhuo Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Zhi-Wei Bai
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yong Ling
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Li-Qin He
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Peng Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Hong-Xia Gu
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Rong-Feng Hu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Li-Qin He.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Additional information

    These authors contributed equally: Zhuo Zhang, Zhi-Wei Bai.

    Electronic supplementary material

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Zhang, Z., Bai, ZW., Ling, Y. et al. Design, synthesis and biological evaluation of novel furoxan-based coumarin derivatives as antitumor agents. Med Chem Res 27, 1198–1205 (2018). https://doi.org/10.1007/s00044-018-2140-x

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00044-018-2140-x

    Keywords

    Search

    Navigation