title: 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.
authors.affiliation: Istituto CNR per la Sintesi Organica e Fotoreattività I.S.O.F., Area della Ricerca di Bologna, Via P. Gobetti 101, 40129 Bologna, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Samorì
authors.forename: Andrea
authors.initials: A
authors.lastname: Guerrini
authors.forename: Greta
authors.initials: G
authors.lastname: Varchi
authors.forename: Gabriele
authors.initials: G
authors.lastname: Fontana
authors.forename: Ezio
authors.initials: E
authors.lastname: Bombardelli
authors.forename: Stella
authors.initials: S
authors.lastname: Tinelli
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Beretta
authors.forename: Serena
authors.initials: S
authors.lastname: Basili
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
authors.forename: Arturo
authors.initials: A
authors.lastname: Battaglia
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D008958:Models, Molecular; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin