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  • Title: Synthesis of new camptothecin analogs with improved antitumor activities.
    Author: Niizuma S, Tsukazaki M, Suda H, Murata T, Ohwada J, Ozawa S, Fukuda H, Murasaki C, Kohchi M, Morikami K, Yoshinari K, Endo M, Ura M, Tanimura H, Miyazaki Y, Takasuka T, Kawashima A, Nanba E, Nakano K, Ogawa K, Kobayashi K, Okabe H, Umeda I, Shimma N.
    Journal: Bioorg Med Chem Lett; 2009 Apr 01; 19(7):2018-21. PubMed ID: 19254843.
    Abstract:
    Novel hexacyclic camptothecin analogs containing cyclic amidine, urea, or thiourea moiety were designed and synthesized based on the proposed 3D-structure of the topoisomerase I (Topo I)/DNA/camptothecin ternary complex. The analogs were prepared from 9-nitrocamptothecin via 7,9-diaminocamptothecin derivatives as a key intermediate. Among them, 7c exhibited in vivo antitumor activities superior to CPT-11 in human cancer xenograft models in mice at their maximum tolerated doses though its in vitro antiproliferative activity was comparable to SN-38 against corresponding cell lines.
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