title: Stereoelectronic factors influencing the biological activity and DNA interaction of synthetic antitumor agents modeled on CC-1065.
abstract: The synthesis, physicochemical properties, and biological activities of a series of novel spiro cyclopropyl compounds, modeled on the potent antitumor antibiotic CC-1065 (1), are described. Many of these synthetic analogues are significantly more effective than 1 against murine tumors. In particular, compound 27 exhibits high activity and potency. Structure-activity analysis supports a molecular mechanism for biological action involving hydrophobic interaction of the drug with DNA and acid-catalyzed alkylation of DNA.
authors.affiliation: Research Laboratories, Upjohn Company, Kalamazoo, Michigan 49001.
authors.forename: M A
authors.initials: MA
authors.lastname: Warpehoski
authors.forename: I
authors.initials: I
authors.lastname: Gebhard
authors.forename: R C
authors.initials: RC
authors.lastname: Kelly
authors.forename: W C
authors.initials: WC
authors.lastname: Krueger
authors.forename: L H
authors.initials: LH
authors.lastname: Li
authors.forename: J P
authors.initials: JP
authors.lastname: McGovren
authors.forename: M D
authors.initials: MD
authors.lastname: Prairie
authors.forename: N
authors.initials: N
authors.lastname: Wicnienski
authors.forename: W
authors.initials: W
authors.lastname: Wierenga
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D000080890:Duocarmycins; D005260:Female; D007211:Indoles; D007933:Leucomycins / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008811:Mice, Inbred DBA; D012995:Solubility
chemical_list: D000903:Antibiotics, Antineoplastic; D000080890:Duocarmycins; D007211:Indoles; D007933:Leucomycins; C018782:CC 1065; D004247:DNA