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

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Samorì C,Guerrini A,Varchi G,Fontana G,Bombardelli E,Tinelli S,Beretta GL,Basili S,Moro S,Zunino F,Battaglia A

doi

10.1021/jm801153y

subject

Has Abstract

pub_date

2009-02-26 00:00:00

pages

1029-39

issue

4

eissn

0022-2623

issn

1520-4804

pii

10.1021/jm801153y

journal_volume

52

pub_type

杂志文章

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