Skip to main content
SpringerLink
Log in

Synthesis of new O-alkyl and alkyne–azide cycloaddition derivatives of 4′-methoxy licoflavanone: a distinct prenylated flavonoids depicting potent cytotoxic activity

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

Abstract

Prenylated flavonoids represent a unique class of naturally occurring compounds and have proved to be an important source of chemically diverse novel metabolites. Nevertheless, they possess wild array of biological activities. 4′-Methoxy licoflavanone is a prenylated flavonoid isolated from stem bark of Erytherina subrossa. Herein, we report the synthesis of O-alkyl analogs (2a–2m) and 1,2,3 triazole conjugate (3–14) of 4′-methoxy licoflavanone by selective modification at C-7 position in the chromane nucleus. In addition, all the derivatives were evaluated for in vitro antiproliferative activity against a panel of cancer cell lines including pancreatic cancer (Mia PaCa-2), prostate cancer (PC-3), and human leukemia (HL-60) cells. The results revealed that some analogs including 2e and 2m exhibited better cytotoxicity effect than parent compound, specifically on Mia PaCa-2 cell lines.

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

Similar content being viewed by others

References

  • Aher NG, Pore VS, Mishra NN, Kumar A, Shukla PK, Sharma A, Bhat MK (2009) Synthesis and antifungal activity of 1,2,3-triazole containing new fluconazole analogues. Bioorg Med Chem Lett 19:759–763

    Article  CAS  PubMed  Google Scholar 

  • Barron D, Ibrahim RK (1996) Isoprenylated flavonoids-a survey. Phytochemistry 43:921–982

    Article  CAS  Google Scholar 

  • Barron D, Balland C, Possety F, Ravanel P, Desfougeres A (1996) Flavonoïdes prénylés et perméabilité membranaire. Acta Bot Gall 143:509–520

    Article  CAS  Google Scholar 

  • Beutler JA, Hamel E, Vlietinck AJ, Haemers A, Rajan P, Roitman JN, Cardellina JH II, Boyd MR (1998) Structure-activity requirements for flavone cytotoxicity and binding to tubulin. J Med Chem 41:2333–2338

    Article  CAS  PubMed  Google Scholar 

  • Botta B, Vitalib A, Menendezc P, Misitia D, Monachea GD (2005) Prenylated flavonoids: pharmacology and biotechnology. Curr Med Chem 12:713–739

    Article  CAS  Google Scholar 

  • Brase S, Gil C, Knepper K, Zimmermann V (2005) Organic azides: an exploding diversity of a unique class of compounds. Angew Chem Int Ed 44:5188–5240

    Article  CAS  Google Scholar 

  • Clardy J, Walsh C (2004) Lessons from natural molecules. Nature 432:829–837

    Article  CAS  PubMed  Google Scholar 

  • Dalvie DK, Kalgutkar AS, Khojasteh-Bakht SC, Obach RS, Donnell JP (2002) Biotransformation reactions of five-membered aromatic heterocyclic rings. Chem Res Toxicol 15:269–299

    Article  CAS  PubMed  Google Scholar 

  • Epstein RJ (1990) Drug-induced DNA damage and tumor chemosensitivity. J Clin Oncol 8:2062–2084

    CAS  PubMed  Google Scholar 

  • Jang JP, Na MK, Thuong PT, Njamen D, Mbafor JT, Fomum ZT, Woo ER, Oh WK (2008) Prenylated flavonoids with PTP1B inhibitory activity from the root bark of Erythrina mildbraedii. Chem Pharm Bull 56:85–88

    Article  CAS  PubMed  Google Scholar 

  • Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40:2004–2021

    Article  CAS  Google Scholar 

  • Kumar S, Pathania AS, Saxena AK, Vishwakarma RA, Ali A, Bhushan S (2013) The anticancer potential of flavonoids isolated from the stem bark of Erythrina suberosa through induction of apoptosis and inhibition of STAT signaling pathway in human leukemia HL-60 cells. Chem Biol Interact 205:128–137

    Article  CAS  PubMed  Google Scholar 

  • Liu Q, Tor Y (2003) Simple conversion of aromatic amines into azides. Org Lett 5:2571–2572

    Article  CAS  PubMed  Google Scholar 

  • Meldal M, Tornøe CW (2008) Cu-catalyzed azide-alkyne cycloaddition. Chem Rev 108:2952–3015

    Article  CAS  PubMed  Google Scholar 

  • Miranda CL, Stevens JF, Helmrich A, Henderson MC, Rodriguez RJ, Yang YH, Deinzer ML, Barnes DW, Buhler DR (1999) Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Food Chem Toxicol 37:271–285

    Article  CAS  PubMed  Google Scholar 

  • Mishra BB, Tiwari VK (2011) Natural products: an evolving role in future drug discovery. Eur J Med Chem 46:4769–4807

    Article  CAS  PubMed  Google Scholar 

  • Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 9:231–241

    Article  CAS  PubMed  Google Scholar 

  • Thirumurugan P, Matosiuk D, Jozwiak K (2013) Click chemistry for drug development and diverse chemical–biology applications. Chem Rev 113:4905–4979

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The research leading to these results has received financial support by the Council of Scientific and Industrial Research (CSIR) - India. The authors S. K and A. S. P are thankful to CSIR for providing Senior Research Fellowship. The authors further thank to the analytical department of our institute for providing analytical support.

Author information

Authors and Affiliations

  1. Natural Products Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India

    Sunil Kumar, Yedu K. Nalli, R. A. Vishwakarma & Asif Ali

  2. Cancer Pharmacology Division, Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India

    Anup S. Pathania & Fayaz A. Malik

Authors
  1. Sunil Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anup S. Pathania
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yedu K. Nalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fayaz A. Malik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. A. Vishwakarma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Asif Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Asif Ali.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, S., Pathania, A.S., Nalli, Y.K. et al. Synthesis of new O-alkyl and alkyne–azide cycloaddition derivatives of 4′-methoxy licoflavanone: a distinct prenylated flavonoids depicting potent cytotoxic activity. Med Chem Res 24, 669–683 (2015). https://doi.org/10.1007/s00044-014-1177-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-014-1177-8

Keywords

Search

Navigation