title: Synthesis and preliminary cytotoxicity study of glucuronide derivatives of CC-1065 analogues.
abstract: Glucuronide derivatives of CBI-bearing CC-1065 analogues have been synthesized, and their cytotoxicities tested against U937 leukemia cells. The new compounds show potent antitumor activity in vitro. Compounds 1 and 2, and their corresponding glucuronides 3 and 4 have IC(50) values of 0.6, 0.1, 1.4 and 0.6 nM, respectively. Glucuronide 3 is approximately 2-fold less toxic than its hydroxyl counterpart 1, and glucuronide 4 is approximately 6-fold less toxic than its hydroxyl counterpart 2. Glucuronides 3 and 4 may have limited use in the ADEPT approach. However, they may be used as antitumor agents in a conventional way.
authors.affiliation: Panorama Research, Inc., 2462 Wyandotte Street, Mountain View, CA 94043, USA. yuquiangwang@worldnet.att.net
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Huiling
authors.initials: H
authors.lastname: Yuan
authors.forename: Susan C
authors.initials: SC
authors.lastname: Wright
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: James W
authors.initials: JW
authors.lastname: Larrick
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D000080890:Duocarmycins; D005966:Glucuronidase / Q000378:metabolism; D020719:Glucuronides / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007211:Indoles; D007933:Leucomycins / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D000080890:Duocarmycins; D020719:Glucuronides; D007202:Indicators and Reagents; D007211:Indoles; D007933:Leucomycins; C018782:CC 1065; D005966:Glucuronidase