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  • Title: Synthesis and biological evaluation of 11-substituted 6-aminobenzo[c]phenanthridine derivatives, a new class of antitumor agents.
    Author: Kock I, Heber D, Weide M, Wolschendorf U, Clement B.
    Journal: J Med Chem; 2005 Apr 21; 48(8):2772-7. PubMed ID: 15828815.
    Abstract:
    The synthesis of 11-substituted 6-amino-11,12-dihydrobenzo[c]phenanthridines and 11-substituted 6-aminobenzo[c]phenanthridines through an efficient method is described. The antiproliferative activity of selected compounds against a wide panel of tumor cell lines was tested in the in vitro anticancer screening and the in vivo hollow fiber assay of the National Cancer Institute. Several compounds turned out to exhibit considerable cytotoxicity for tumor cells. For the study of structure-activity relationships different substituents were introduced in the 11-position. Compounds with methoxyphenyl substituents tended to show the highest potency. Several compounds exhibited noteworthy antitumor activity with GI(50) values across all cell lines <1 microM. 6-Amino-11-(3,4,5-trimethoxyphenyl)benzo[c]phenanthridine perchlorate was the most potent agent in the NCI's in vivo hollow fiber assay. Most of the tested compounds showed a remarkable selectivity for leukemia, breast cancer, and prostate cancer.
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