CC-1065 analogues bearing different DNA-binding subunits: synthesis, antitumor activity, and preliminary toxicity study.
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.
Wang
Yuqiang
Y
Panorama Research, Inc., 2462 Wyandotte Street, Mountain View, California 94043, USA. yuqiang.wang@worldnet.att.net
Li
Lianfa
L
Ye
Wenqing
W
Tian
Zhiming
Z
Jiang
Wei
W
Wang
Hong
H
Wright
Susan C
SC
Larrick
James W
JW
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
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