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  • Title: Design, synthesis and in vitro cytotoxic studies of novel bis-pyrrolo[2,1][1,4] benzodiazepine-pyrrole and imidazole polyamide conjugates.
    Author: Kumar R, Lown JW.
    Journal: Eur J Med Chem; 2005 Jul; 40(7):641-54. PubMed ID: 15935899.
    Abstract:
    The design, synthesis and biological evaluation of novel pyrrolo [2,1][1,4] benzodiazepine (PBD) dimers 38-43 linked with pyrrole and imidazole polyamides from either side by a flexible methylene chain of variable length are described, which involved mercuric chloride mediated cyclization of the corresponding amino diethyl thioacetals. The compounds were prepared with varying numbers of pyrrole and imidazole containing polyamides to determine the structural requirements for optimal in vitro antitumor activity. These compounds were tested against a panel of 60 human cancer cells by the National Cancer Institute, and demonstrated that, of the compounds bis-PBD-pyrrole polyamides (38-40) and bis-PBD-imidazole polyamides (41-43) certain of the bis-PBD-pyrrole and imidazole polyamide conjugates are active for individual cancer cell lines (Table 1). However, this study found that bis-PBD-pyrrole and imidazole polyamide conjugates 38-43 in general are potent against many human cancer cell lines.
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