title: Design, synthesis, and biological evaluation of achiral analogs of duocarmycin SA.
abstract: The design, synthesis, as well as biochemical and biological evaluation of two novel achiral analogs of duocarmycin SA (DUMSA), 1 and 2, are described. Like CC-1065 and adozelesin, compounds 1 and 2 covalently reacted with adenine-N3 in AT-rich sequences and led to the formation of DNA strand breaks upon heating. The cytotoxicity of compounds 1 and 2 against human cancer cells (K562, LS174T) was determined using a MTT assay giving IC(50) values in the low nanomolar. Further cytotoxicity screening of compound 2 conducted by the NCI against a panel of 60 different human cancer cell lines indicated that it was particularly active against several solid tumor cells lines derived from the lung, colon, CNS, skin, and breast.
authors.affiliation: Department of Chemistry, Furman University, Greenville, SC 29613, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Daniell
authors.forename: Michelle
authors.initials: M
authors.lastname: Stewart
authors.forename: Erik
authors.initials: E
authors.lastname: Madsen
authors.forename: Minh
authors.initials: M
authors.lastname: Le
authors.forename: Heather
authors.initials: H
authors.lastname: Handl
authors.forename: Natalie
authors.initials: N
authors.lastname: Brooks
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kiakos
authors.forename: John A
authors.initials: JA
authors.lastname: Hartley
authors.forename: Moses
authors.initials: M
authors.lastname: Lee
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D004249:DNA Damage; D017931:DNA Primers; D004353:Drug Evaluation, Preclinical; D000080890:Duocarmycins; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D000080890:Duocarmycins; D007211:Indoles; D011758:Pyrroles; C066098:duocarmycin SA