Semisynthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins

Cristian Samorì, Andrea Guerrini, Greta Varchi, Gabriele Fontana, Ezio Bombardelli, Stella Tinelli, Giovanni Luca Beretta, Serena Basili, Stefano Moro, Franco Zunino, Arturo Battaglia

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Abstract

The synthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins are reported. A general synthetic protocol, based on "C-5 camptothecin (C-5-CPT) enolate chemistry", allows one to obtain various C5-substituted analogues. All new compounds, obtained as 1:1 epimeric mixtures, were tested for their antiproliferative activity. Experimental data showed that all novel derivatives are less active than the reference compounds and that one of the two epimers is more active than the other. Molecular docking simulations were performed to achieve more insight into the interactions between the new C5- modified CPTs and Topo I. A good correlation was observed when the data of cytotoxicity and the values calculated for the free binding energy were combined.

Original languageEnglish
Pages (from-to)1029-1039
Number of pages11
JournalJournal of Medicinal Chemistry
Volume52
Issue number4
DOIs
Publication statusPublished - Feb 26 2009

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Samorì, C., Guerrini, A., Varchi, G., Fontana, G., Bombardelli, E., Tinelli, S., Beretta, G. L., Basili, S., Moro, S., Zunino, F., & Battaglia, A. (2009). Semisynthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins. Journal of Medicinal Chemistry, 52(4), 1029-1039. https://doi.org/10.1021/jm801153y