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

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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.

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Fig. 1
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Scheme 1
Scheme 2
Scheme 3

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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

References

  • Cao ZS (2008) Methods of making ester camptothecins WO patent 2008-021015, filed 2 August 2007, issued 21 February 2008

  • 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 2003

  • 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 41:31–37

    Article  CAS  PubMed  Google Scholar 

  • Essers M, Wibbeling B, Haufe G (2001) Synthesis of the first fluorinated cantharidin analogues. Tetrahedron Lett 42:5429–5433

    Article  CAS  Google Scholar 

  • Gupta P, Mahajan A (2017) Shades of chemical beauty: An overview of synthetic routes to some anticancer drugs. Synth Commun 47:1415–1433

    Article  CAS  Google Scholar 

  • 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 17:3392–3397

    Article  CAS  PubMed  Google Scholar 

  • 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 18:1335–1338

    Article  CAS  Google Scholar 

  • 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 35:957–964

    Article  CAS  Google Scholar 

  • 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 56:7902–7910

    Article  CAS  PubMed  Google Scholar 

  • Vishnuvajjala BR, Garzon-Aburbeh A (1990) Water soluble prodrugs of camptothecin. US patent 1990-4943579, filed 6 October 1987, issued 24 July 1990

  • Yadav DK, Khan F (2013) QSAR, docking and ADMET studies of camptothecin derivatives as inhibitors of DNA topoisomerase-I. J Chemom 27:21–33

    Article  CAS  Google Scholar 

  • 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 65:4601–4606

    Article  CAS  PubMed  Google Scholar 

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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.

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Authors and Affiliations

  1. School of Pharmacy, Zunyi Medical University, No. 6 Xue Fu West Road, Xin Pu New District, Zunyi City, Guizhou Province, 563003, China

    Xian H. Wang, Fu H. Yang, Chang K. Zhao, Lei Gao & Chan Li

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  1. Xian H. Wang
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  2. Fu H. Yang
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  3. Chang K. Zhao
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  4. Lei Gao
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  5. Chan Li
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Correspondence to Chang K. Zhao.

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Wang, X.H., Yang, F.H., Zhao, C.K. et al. Sealed tube promoted coupling of camptothecin and norcantharidin acid ester and their preliminary biological activity evaluation in vitro. Med Chem Res 27, 406–411 (2018). https://doi.org/10.1007/s00044-017-2066-8

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  • DOI: https://doi.org/10.1007/s00044-017-2066-8

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