title: CC-1065 analogues bearing different DNA-binding subunits: synthesis, antitumor activity, and preliminary toxicity study.
abstract: CC-1065 analogues bearing different DNA-binding subunits were synthesized. A terminal C5-NO2 and -F moiety at the DNA-binding subunit increased the drug's potency and antitumor efficacy. A C5-OCH3 reduced the potency and antitumor efficacy. Compound (+/-)-7, bearing a trans double bond, had increased antitumor efficacy. A preliminary toxicity study indicated that terminal C5-OCH3 and -acetamido moieties at the DNA-binding subunit caused delayed death in mice.
authors.affiliation: Panorama Research, Inc., 2462 Wyandotte Street, Mountain View, California 94043, USA. yuqiang.wang@worldnet.att.net
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Lianfa
authors.initials: L
authors.lastname: Li
authors.forename: Wenqing
authors.initials: W
authors.lastname: Ye
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Tian
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Susan C
authors.initials: SC
authors.lastname: Wright
authors.forename: James W
authors.initials: JW
authors.lastname: Larrick
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004247:DNA / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D000080890:Duocarmycins; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D007933:Leucomycins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015996:Survival Rate; D023382:Toxicity Tests, Acute
chemical_list: C471873:3-(5-(5-acetylaminoindol-2-yl)amidoindol-2-yl)-1-chloromethyl-5-hydroxybenz(g)indole; D000970:Antineoplastic Agents; D000080890:Duocarmycins; D007211:Indoles; D007933:Leucomycins; C018782:CC 1065; D004247:DNA