Synthesis and cytotoxic activity of new 9-substituted camptothecins

Sabrina Dallavalle, Daniela Granza Rocchetta, Loana Musso, Lucio Merlini, Gabriella Morini, Sergio Penco, Stella Tinelli, Giovanni Luca Beretta, Franco Zunino

Research output: Contribution to journalArticle

Abstract

A series of novel 9-substituted camptothecins derived from 9-formylcamptothecin were synthesized. The aldehyde was obtained from 10-hydroxycamptothecin or, better, by total synthesis. The compounds showed antiproliferative activity higher than that of the reference compound topotecan. Modelling suggested the possibility of a favourable interaction of small and polar 9-substituents with the topoisomerase I-DNA complex, which is consistent with the higher activity of these derivatives with respect to the corresponding 7-substituted camptothecins.

Original languageEnglish
Pages (from-to)2781-2787
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number9
DOIs
Publication statusPublished - May 1 2008

Fingerprint

Camptothecin
Topotecan
Type I DNA Topoisomerase
Aldehydes
Derivatives
10-hydroxycamptothecin

Keywords

  • Antitumor agents
  • Camptothecin
  • DNA cleavage
  • Synthesis
  • Topoisomerase I

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Dallavalle, S., Rocchetta, D. G., Musso, L., Merlini, L., Morini, G., Penco, S., ... Zunino, F. (2008). Synthesis and cytotoxic activity of new 9-substituted camptothecins. Bioorganic and Medicinal Chemistry Letters, 18(9), 2781-2787. https://doi.org/10.1016/j.bmcl.2008.04.016

Synthesis and cytotoxic activity of new 9-substituted camptothecins. / Dallavalle, Sabrina; Rocchetta, Daniela Granza; Musso, Loana; Merlini, Lucio; Morini, Gabriella; Penco, Sergio; Tinelli, Stella; Beretta, Giovanni Luca; Zunino, Franco.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 9, 01.05.2008, p. 2781-2787.

Research output: Contribution to journalArticle

Dallavalle, S, Rocchetta, DG, Musso, L, Merlini, L, Morini, G, Penco, S, Tinelli, S, Beretta, GL & Zunino, F 2008, 'Synthesis and cytotoxic activity of new 9-substituted camptothecins', Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 9, pp. 2781-2787. https://doi.org/10.1016/j.bmcl.2008.04.016
Dallavalle S, Rocchetta DG, Musso L, Merlini L, Morini G, Penco S et al. Synthesis and cytotoxic activity of new 9-substituted camptothecins. Bioorganic and Medicinal Chemistry Letters. 2008 May 1;18(9):2781-2787. https://doi.org/10.1016/j.bmcl.2008.04.016
Dallavalle, Sabrina ; Rocchetta, Daniela Granza ; Musso, Loana ; Merlini, Lucio ; Morini, Gabriella ; Penco, Sergio ; Tinelli, Stella ; Beretta, Giovanni Luca ; Zunino, Franco. / Synthesis and cytotoxic activity of new 9-substituted camptothecins. In: Bioorganic and Medicinal Chemistry Letters. 2008 ; Vol. 18, No. 9. pp. 2781-2787.
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