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. 2015 May 21;20(5):9393-404.
doi: 10.3390/molecules20059393.

Synthesis and Biological Evaluation of Novel Water-Soluble Poly-(ethylene glycol)-10-hydroxycamptothecin Conjugates

Na Guo  1 , Du Jiang  2 , Luyao Wang  3 , Xing You  4 , Yu-Ou Teng  5 , Peng Yu  6
Affiliations

Synthesis and Biological Evaluation of Novel Water-Soluble Poly-(ethylene glycol)-10-hydroxycamptothecin Conjugates

Na Guo et al. Molecules. .

Abstract

In order to improve the antitumor activity and water solubility of 10-hydroxycamptothecin (HCPT), a series of novel HCPT conjugates were designed and synthesized by conjugating polyethylene glycol (PEG) to the 10-hydroxyl group of HCPT via a valine spacer. The in vitro stability of these synthesized compounds was determined in pH 7.4 buffer at 37 °C, and the results showed that they released HCPT at different rates. All the compounds demonstrated significant antitumor activity in vitro against K562, HepG2 and HT-29 cells. Among them, compounds, 4a, 4d, 4e and 4f, exhibited 2-5 times higher potency than HCPT. The stability and antitumor activity of these conjugates were found to be closely related to the length of PEG and the linker type, conjugates with a relatively short PEG chain and carbamate linkages (compounds 4a and 4f) exhibited controlled release of HCPT and excellent antitumor in vitro activity.

Keywords: PEG; antitumor; conjugate; hydroxycamptothecin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of HCPT, HCPT-valine methyl ester, irinotecan and SN38.
Figure 2
Figure 2
Structures of conjugates 4a–4f, 5, and 6.
Scheme 1
Scheme 1
Synthesis of conjugates 4a–4f.
Scheme 2
Scheme 2
Synthesis of conjugate 5.
Scheme 3
Scheme 3
Synthesis of conjugate 6.
See this image and copyright information in PMC

References

    1. Ohwada J., Ozawa S., Kohchi M. Synthesis and biological activities of a pH-dependently activated water-soluble prodrug of a novel hexacyclic camptothecin analog. Bioorg. Med. Chem. Lett. 2009;19:2772–2776. - PubMed
    1. Basili S., Moro S. Novel camptothecin derivatives as topoisomerase I inhibitors. Expert Opin. Ther. Patents. 2009;19:555–574. doi: 10.1517/13543770902773437. - DOI - PubMed
    1. Wang J.Q., Sun X.R., Mao W.W., Sun W.L., Tang J.B., Sui M.H., Shen Y.Q., Gu Z.W. Tumor redox heterogeneity-responsive prodrug nanocapsules for cancer chemotherapy. Adv. Mater. 2013;25:3670–3676. doi: 10.1002/adma.201300929. - DOI - PubMed
    1. Shamay Y., Paulin D., Ashkenasy G., David A. E-selectin binding peptide-polymer-drug conjugates and their selective cytotoxicity against vascular endothelial cells. Biomaterials. 2009;30:6460–6468. doi: 10.1016/j.biomaterials.2009.08.013. - DOI - PubMed
    1. Xu Z.G., Wang D.D., Xu S., Liu X.Y., Zhang X.Y., Zhang H.X. Preparation of camptothecin prodrug with glutathione-responsive disulfide linker for anticancer drug delivery. Chem. Asian J. 2014;9:199–205. doi: 10.1002/asia.201301030. - DOI - PubMed

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