Synthesis and cytotoxic activity of new 9-substituted camptothecins.
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.
Dallavalle
Sabrina
S
Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133 Milano, Italy. sabrina.dallavalle@unimi.it
Rocchetta
Daniela Granza
DG
Musso
Loana
L
Merlini
Lucio
L
Morini
Gabriella
G
Penco
Sergio
S
Tinelli
Stella
S
Beretta
Giovanni Luca
GL
Zunino
Franco
F
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
D000972:Antineoplastic Agents, Phytogenic; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin