title: Synthesis and cytotoxic activity of new 9-substituted camptothecins.
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.
authors.affiliation: Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133 Milano, Italy. sabrina.dallavalle@unimi.it
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dallavalle
authors.forename: Daniela Granza
authors.initials: DG
authors.lastname: Rocchetta
authors.forename: Loana
authors.initials: L
authors.lastname: Musso
authors.forename: Lucio
authors.initials: L
authors.lastname: Merlini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Morini
authors.forename: Sergio
authors.initials: S
authors.lastname: Penco
authors.forename: Stella
authors.initials: S
authors.lastname: Tinelli
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Beretta
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin