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 compds. showed antiproliferative activity higher than that of the ref. compd. topotecan. Modeling suggested the possibility of a favorable interaction of small and polar 9-substituents with the topoisomerase I-DNA complex, which is consistent with the higher activity of these derivs. with respect to the corresponding 7-substituted camptothecins.
Titolo: | Synthesis and cytotoxic activity of new 9-substituted camptothecins |
Autori: | |
Parole Chiave: | Antitumor agents; Camptothecin; DNA cleavage; Synthesis; Topoisomerase I |
Settore Scientifico Disciplinare: | Settore CHIM/06 - Chimica Organica Settore CHIM/08 - Chimica Farmaceutica |
Data di pubblicazione: | 1-mag-2008 |
Rivista: | |
Tipologia: | Article (author) |
Digital Object Identifier (DOI): | 10.1016/j.bmcl.2008.04.016 |
Appare nelle tipologie: | 01 - Articolo su periodico |
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