title: Establishing the parabolic relationship between reactivity and activity for derivatives and analogues of the duocarmycin and CC-1065 alkylation subunits.
abstract: The preparation of a novel series of N-aryl CBI derivatives is detailed in which an aryl para substituent could be used to predictably modulate the reactivity of the resulting CC-1065/duocarmycin alkylation subunit analogue (rho = 0.17). The derivatives were found to be exceptionally stable and to exhibit a well-defined relationship between reactivity and cytotoxic potency. When combined with the results of an extensive series of N-acyl CBI analogues and derivatives assembled over the past 15 years, the studies define a fundamental parabolic relationship between reactivity and cytotoxic potency.
authors.affiliation: Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Jay P
authors.initials: JP
authors.lastname: Parrish
authors.forename: Terry V
authors.initials: TV
authors.lastname: Hughes
authors.forename: Inkyu
authors.initials: I
authors.lastname: Hwang
authors.forename: Dale L
authors.initials: DL
authors.lastname: Boger
mesh_terms: D000478:Alkylation; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D000080890:Duocarmycins; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D011760:Pyrrolidinones / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000903:Antibiotics, Antineoplastic; D000080890:Duocarmycins; D007211:Indoles; D011760:Pyrrolidinones; C018782:CC 1065