TY - JOUR
T1 - Semisynthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins
AU - Samorì, Cristian
AU - Guerrini, Andrea
AU - Varchi, Greta
AU - Fontana, Gabriele
AU - Bombardelli, Ezio
AU - Tinelli, Stella
AU - Beretta, Giovanni Luca
AU - Basili, Serena
AU - Moro, Stefano
AU - Zunino, Franco
AU - Battaglia, Arturo
PY - 2009/2/26
Y1 - 2009/2/26
N2 - 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.
AB - 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.
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U2 - 10.1021/jm801153y
DO - 10.1021/jm801153y
M3 - Article
C2 - 19530720
AN - SCOPUS:64349103354
VL - 52
SP - 1029
EP - 1039
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 4
ER -