In contrast to five-membered E-ring analogues, 7-oxyiminomethyl derivatives of homocamptothecins showed ability to form stable ternary complexes with DNA and topoisomerase I. The 7-oxyiminomethyl derivatives of homocamptothecins were evaluated as a racemic mixture. Following the isolation of the two enantiomers, the 20 (R)-hydroxy isomer confirms the best activity. By using a panel of human tumor cells, all tested homocamptothecins showed a potent antiproliferative activity, correlating to the persistence of the cleavable complex. No significant difference was observed between the natural scaffold and the corresponding homocamptothecin homologue. A selected compound of this series exhibited an excellent antitumor activity against human gastrointestinal tumor xenografts. (C) 2008 Elsevier Ltd. All rights reserved.
Giannini G, Marzi M, Cabri W, Marastoni E, Battistuzzi G, Vesci L, et al. (2008). E-ring-modified 7-oxyiminomethyl camptothecins: Synthesis and preliminary in vitro and in vivo biological evaluation. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 18(9), 2910-2915 [10.1016/j.bmcl.2008.03.074].
E-ring-modified 7-oxyiminomethyl camptothecins: Synthesis and preliminary in vitro and in vivo biological evaluation
Cabri W;
2008
Abstract
In contrast to five-membered E-ring analogues, 7-oxyiminomethyl derivatives of homocamptothecins showed ability to form stable ternary complexes with DNA and topoisomerase I. The 7-oxyiminomethyl derivatives of homocamptothecins were evaluated as a racemic mixture. Following the isolation of the two enantiomers, the 20 (R)-hydroxy isomer confirms the best activity. By using a panel of human tumor cells, all tested homocamptothecins showed a potent antiproliferative activity, correlating to the persistence of the cleavable complex. No significant difference was observed between the natural scaffold and the corresponding homocamptothecin homologue. A selected compound of this series exhibited an excellent antitumor activity against human gastrointestinal tumor xenografts. (C) 2008 Elsevier Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
