Advertisement

Medicinal Chemistry Research

, Volume 27, Issue 2, pp 406–411 | Cite as

Sealed tube promoted coupling of camptothecin and norcantharidin acid ester and their preliminary biological activity evaluation in vitro

  • Xian H. Wang
  • Fu H. Yang
  • Chang K. Zhao
  • Lei Gao
  • Chan Li
Original Research

Abstract

A facile synthetic method was developed for the novel acid-sensitive camptothecin norcantharidin acid ester derivatives 3 in sealed tube. This method offers several advantages including high yield and simple work procedure which can be extended for the synthesis of analogs. The new synthetic compounds 3 have shown better activity against several tumor cell lines in vitro test.

Keywords

Sealed tube Camptothecin Norcantharidin Coupling Anticancer Synthesis 

Abbreviations

CPT

Camptothecin

TMS

Tetramethylsilane

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

EDCI

(3-dimethylaminopropyl) ethyl-carbodiimide monohydrochloride

DMAP

4-dimethylaminopyridine

Notes

Acknowledgements

I am very grateful for the finacial support from Joint fund project of Guizhou Provincial department of Science and Technology (QianKeHe LH Zi [2014]7545), (QianKeHe LH Zi [2015]7531), Science and Technology Department of Guizhou Province (QKHSY [2017]2844) and (QKHSY [2015]3030). I am also thankful for Dr. Yuqi He’s useful explanation on HPLC and LC/MS spectra data.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_2066_MOESM1_ESM.doc (1.6 mb)
Supplementary Information

References

  1. Cao ZS (2008) Methods of making ester camptothecins WO patent 2008-021015, filed 2 August 2007, issued 21 February 2008Google Scholar
  2. Cao ZS, Giovanella BC (2003) Halo-alkyl esters of camptothecin and methods of treating cancer using these compounds. US patent 2003-0212087, filed 6 May 2002, issued 13 November 2003Google Scholar
  3. Cao ZS, Harris N, Kozielski A, Vardeman D, Stehlin JS, Giovanella B (1998) Alkyl esters of camptothecin and 9-nitrocamptothecin: Synthesis, in vitro pharmacokinetics, toxicity, and antitumor activity. J Med Chem 41:31–37CrossRefPubMedGoogle Scholar
  4. Essers M, Wibbeling B, Haufe G (2001) Synthesis of the first fluorinated cantharidin analogues. Tetrahedron Lett 42:5429–5433CrossRefGoogle Scholar
  5. Gupta P, Mahajan A (2017) Shades of chemical beauty: An overview of synthetic routes to some anticancer drugs. Synth Commun 47:1415–1433CrossRefGoogle Scholar
  6. Hill TA, Stewart SG, Sauer B, Gilbert J, Ackland SP, Sakoff JA, McCluskey A (2007) Heterocyclic substituted cantharidin and norcantharidin analogues-synthesis, protein phosphatase (1 and 2A) inhibition, and anti-cancer activity. Bioorg Med Chem Lett 17:3392–3397CrossRefPubMedGoogle Scholar
  7. Li DZ, Li Y, Chen XG, Zhu CG, Yang J, Liu HY, Pan XD (2007) Synthesis and antitumor activity of heterocyclic acid ester derivatives of 20S-camptothecins. Chin Chem Lett 18:1335–1338CrossRefGoogle Scholar
  8. McCluskey A, Keane MA, Mudgee LM, Sim ATR, Quinn RJ (2000) Anhydride modified cantharidin analogues. Is ring opening important in the inhibition of protein phosphatase 2A? Eur J Med Chem 35:957–964CrossRefGoogle Scholar
  9. Miao ZY, Zhu LJ, Dong GQ, Zhuang CL, Wu YL, Wang SZ, Guo ZZ, Liu Y, Wu SC, Zhu SP, Fang K, Yao JZ, Li J, Sheng CQ, Zhang WN (2013) A new strategy to improve the metabolic stability of lactone: discovery of (20S,21S)-21-fluoro camptothecins as novel, hydrolytically stable topoisomerase I inhibitors. J Med Chem 56:7902–7910CrossRefPubMedGoogle Scholar
  10. Vishnuvajjala BR, Garzon-Aburbeh A (1990) Water soluble prodrugs of camptothecin. US patent 1990-4943579, filed 6 October 1987, issued 24 July 1990Google Scholar
  11. Yadav DK, Khan F (2013) QSAR, docking and ADMET studies of camptothecin derivatives as inhibitors of DNA topoisomerase-I. J Chemom 27:21–33CrossRefGoogle Scholar
  12. Zhao H, Lee C, Sai P, Choe YH, Boro M, Pendri A, Guan S, Greenwald RB (2000) 20-O acylcamptothecin derivatives: evidence for lactone stabilization. J Org Chem 65:4601–4606CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Xian H. Wang
    • 1
  • Fu H. Yang
    • 1
  • Chang K. Zhao
    • 1
  • Lei Gao
    • 1
  • Chan Li
    • 1
  1. 1.School of PharmacyZunyi Medical UniversityZunyi CityChina

Personalised recommendations