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.
E-ring-modified 7-oxyiminomethyl camptothecins: Synthesis and preliminary in vitro and in vivo biological evaluation / Giannini G; Marzi M; Cabri W; Marastoni E; Battistuzzi G; Vesci L; Pisano C; Beretta GL; De Cesare M; Zunino F. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - ELETTRONICO. - 18:9(2008), pp. 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.