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Ferrocenylchalcone–uracil conjugates: synthesis and cytotoxic evaluation

Medicinal Chemistry Research volume 27, pages 1260–1268 (2018)Cite this article

Abstract

Huisgen’s azide–alkyne cycloaddition reaction was employed to synthesize a series of 1H-1,2,3-triazole-tethered uracil–ferrocenyl chalcone conjugates with the aim of evaluating their in vitro anti-proliferative efficacy on human leukemia (CCRF-CEM) and human breast adenocarcinoma (MDA-MB-468) cell lines. Cytotoxic evaluation studies identified a number of synthesized conjugates that inhibited the proliferation of leukemia cancer cells by ~70% after 72 h. The selected synthesized conjugates were found to be significantly less cytotoxic against normal kidney cell line (LLC-PK1) when compared with CCRF-CEM cancer cells.

Synthesis and in vitro anti-proliferative efficacy of 1H-1,2,3-triazole-tethered uracil–ferrocenylchalcone conjugates on human leukemia (CCRF-CEM) and human breast adenocarcinoma (MDA-MB-468) cell lines.

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Scheme 1
Fig. 1
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Abbreviations

CCRF-CEM:

ATCC No. CCL-119, human leukemia cell line

MDA-MB-468:

ATCC, No. HTB-132, human breast adenocarcinoma

LLC-PK1:

ATCCCL-101, normal kidney cell line

References

  • Allardyce CS, Dorcier A, Scolaro C, Dyson PJ (2005) Development of organometallic (organo-transition metal) pharmaceuticals. Appl Organomet Chem 19:1–10

    Article  CAS  Google Scholar 

  • American Cancer Society (2016) Cancer facts & figures. American Cancer Society, Atlanta, p 1

    Google Scholar 

  • Dezor-Mazur M, Kazmierczak F, Golankiewicz K (1984) Synthesis and spectral properties of some dinucleotide analogues containing bromine in 5-position of pyrimidine moieties. Heterocycles 22:2739–2750

    Article  CAS  Google Scholar 

  • Duivenvoorden WCM, Liu Y, Schatte G, Kraatz HB (2005) Synthesis of redox-active ferrocene pyrazole conjugates and their cytotoxicity in human mammary adenocarcinoma MCF-7 cells. Inorg Chim Acta 358:3183–3189

    Article  CAS  Google Scholar 

  • Fadeyi OO, Adamson ST, Myles EL, Okoro CO (2008) Novel fluorinated acridone derivatives Part 1: synthesis and evaluation as potential anticancer agents. Bioorg Med Chem Lett 18:4172–4176

    Article  CAS  PubMed  Google Scholar 

  • Fiorina VJ, Dubois RJ, Brynes S (1978) Ferrocenyl polyamines as agents for chemoimmunotherapy of cancer. J Med Chem 21:393–395

    Article  CAS  PubMed  Google Scholar 

  • Fouda MFR, Abd-Elzaher MM, Abdelsamaia RA, Labib AA (2007) On the medicinal chemistry of ferrocene. Appl Organomet Chem 21:613–625

    Article  CAS  Google Scholar 

  • Grant SK (2009) Therapeutic protein kinase inhibitors. Cell Mol Life Sci 66:1163–1177

    Article  CAS  PubMed  Google Scholar 

  • Hillard E, Vessieres A, Bideau FLe, Plazuk D, Spera D, Huche M, Jaouen G (2006) A series of unconjugated ferrocenyl phenols: prospects as anticancer agents. Chem Med Chem 1:551–559

    Article  CAS  PubMed  Google Scholar 

  • Kumar K, Carreere-Kremer S, Kremer L, Gueerardel Y, Biot C, Kumar V (2013) 1H-1,2,3-Triazole-tethered Isatin-ferrocene and isatin-ferrocenylchalcone conjugates: synthesis and in vitro anti-tubercular evaluation. Organometallics 32:5713–5719

    Article  CAS  Google Scholar 

  • Kumar K, Kremer SC, Kremer L, Guerardel Y, Biot C, Kumar V (2013) Azide-alkyne cycloaddition en route towards 1H-1,2,3-triazole-tethered β-lactam-ferrocene and β-lactam-ferrocenylchalcone conjugates: synthesis and in vitro anti-tubercular evaluation. Dalton Trans 42:1492–1500

    Article  CAS  PubMed  Google Scholar 

  • Kumar K, Singh P, Kremer L, Guerardel Y, Biot C, Kumar V (2012) 1H-1, 2, 3-Triazole-tethered isatin-ferrocene and isatin-ferrocenylchalcone conjugates: synthesis and in vitro anti-tubercular evaluation. Dalton Trans 41:5778–5781

    Article  CAS  PubMed  Google Scholar 

  • Li DZ, Zhang QZ, Wang CY, Zhang YL, Li XY, Huang JT, Liu HY, Fu ZD, Song HX, Lin JP, Ji TF, Pan XD (2012) Synthesis and antitumor activity of novel substituted uracil-1′(N)-acetic acid ester derivatives of 20(S)-camptothecins. Eur J Med Chem 125:1235

    Article  Google Scholar 

  • Mareel M, Leroy A (2003) Clinical, cellular, and molecular aspects of cancer invasion. Physiol Rev 83:337–376

    Article  CAS  PubMed  Google Scholar 

  • Newkome GR, Pandler WW (1982) Contemporary heterocyclic chemistry. Wiley, New York

    Google Scholar 

  • Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, Nakamura S, Kakinuma S, Iwazaki S, Ishikawa S, Kawate H, Nakajima S, Morishita Y T (2004) Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer. Br J Cancer 90:1003–1010

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Oliveira AC, de, Silva EG, da, Rocha DD, Hillard EA, Pigeon P, Jaouen G, Rodrigues FA, Abreu FC, de, Rocha FF, da, Goulart MO, Costa-Lotufo LV (2014) Molecular mechanism of action of 2-ferroce- nyl-1,1-diphenylbut-1-ene on HL-60 leukemia cells, Chem. Med Chem 9:2580–2586

    Google Scholar 

  • Pan X, Wang C, Wang F, Li P, Hu Z, Shan Y, Zhang J (2011) Development of 5-Fluorouracil derivatives as anticancer agents. Curr Med Chem 18:4538–4556

    Article  CAS  PubMed  Google Scholar 

  • Pettit GR, Rhodes MR, Herald DL, Hamel E, Schmidt JM, Pettit RK (2005) Antineoplastic agents. 445. Synthesis and evaluation of structural modifications of (Z)- and (E)-combretastatin A-41. J Med Chem 48:4087–4099

    Article  CAS  PubMed  Google Scholar 

  • Raj R, Saini A, Gut J, Rosenthal PJ, Kumar V (2015) Synthesis and in vitro antiplasmodial evaluation of 7-chloroquinoline–chalcone and 7-chloroquinoline–ferrocenylchalcone conjugates. Eur J Med Chem 95:230–239

    Article  CAS  PubMed  Google Scholar 

  • Singh A, Gut J, Rosenthal PJ, Kumar V (2017) 4-Aminoquinoline-ferrocenyl-chalcone conjugates: Synthesis and anti-plasmodial evaluation. Eur J Med Chem 125:269–277

    Article  CAS  PubMed  Google Scholar 

  • Singh P, Raj R, Kumar V, Mahajan MP, Bedi PMS, Kaur T, Saxena AK (2012) 1,2,3-Triazole tethered β-lactam-chalcone bifunctional hybrids: synthesis and anticancer evaluation. Eur J Med Chem 47:594–600

    Article  CAS  PubMed  Google Scholar 

  • Singh P, Raj R, Singh P, Gut J, Rosenthal PJ, Kumar V (2014) Urea/oxalamide tethered b-lactam-7-chloroquinoline conjugates: Synthesis and in vitro anti-malarial evaluation. Eur J Med Chem 71:128–134

    Article  CAS  PubMed  Google Scholar 

  • Solyanik GI (2011) Multifactorial nature of tumor drug resistance. Exp Oncol 32:181–185

    Google Scholar 

  • Srinivasan B, Johnson TE, Xing C (2011) Chalcone-based inhibitors against hypoxia-inducible factor 1-structure activity relationship studies. Bioorg Med Chem Lett 21:555–557

    Article  CAS  PubMed  Google Scholar 

  • Tan YL, Pigeon P, Top S, Labbe E, Buriez O, Hillard EA, Vessières A, Amatore C, Leong WK, Jaouen G (2012) Ferrocenyl catechols: synthesis, oxidation chemistry and anti-proliferative effects on MDA-MB-231 breast cancer cells. Dalton Trans 41:7537–7549

    Article  CAS  PubMed  Google Scholar 

  • Vijayaraghavalu S, Peetla C, Lu S, Labhasetwar V (2012) Epigenetic modulation of the biophysical properties of drug-resistant cell lipids to restore drug transport and endocytic functions. Mol Pharm 9:2730–2742

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wesche J, Haglund K, Haugsten EM (2011) Fibroblast growth factors and their receptors in cancer. Biochem J 37:199–213

    Article  Google Scholar 

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Acknowledgements

Financial assistance from University Grants Commission (UGC), New Delhi, India, under UGC-JRF Fellowship (A.S.). Ref. No. 23/12/2012 (ii) EU-V is gratefully acknowledged (AS).

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Authors and Affiliations

  1. Department of Chemistry, Guru Nanak Dev University, Amritsar, Punjab, 143005, India

    Amandeep Singh & Vipan Kumar

  2. Department of Chemistry, Hindu College, Amritsar, Punjab, 143001, India

    Vishu Mehra

  3. Centre for Targeted Drug Delivery, Chapman University School of pharmacy, Irvine, CA, 92618, USA

    Neda Sadeghiani, Saghar Mozaffari & Keykavous Parang

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  1. Amandeep Singh
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  2. Vishu Mehra
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  3. Neda Sadeghiani
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  4. Saghar Mozaffari
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  6. Vipan Kumar
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Correspondence to Vipan Kumar.

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Singh, A., Mehra, V., Sadeghiani, N. et al. Ferrocenylchalcone–uracil conjugates: synthesis and cytotoxic evaluation. Med Chem Res 27, 1260–1268 (2018). https://doi.org/10.1007/s00044-018-2145-5

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  • DOI: https://doi.org/10.1007/s00044-018-2145-5

Keywords

  • Click chemistry
  • Cytotoxic evaluation
  • Ferrocenylchalcone
  • Uracil