Substituent effects within the DNA binding subunit of CBI analogues of the duocarmycins and CC-1065

被引：14
|
作者：
Boger, DL
Stauffer, F
Hedrick, MP
机构：
[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 15期
基金：
美国国家卫生研究院;
关键词：
D O I：
10.1016/S0960-894X(01)00372-9
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of CBI analogues of the duocarmycins and CC-1065 exploring substituent effects within the first indole DNA binding subunit are detailed. Substitution at the indole C5 position led to cytotoxic potency enhancements that are greater than or equal to 1000-fold, providing simplified analogues containing a single DNA binding subunit that are more potent (IC50 = 2-3 pM) than CBI-TMI, duocarmycin SA, or CC-1065. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：2021 / 2024
页数：4
相关论文
共 50 条
  • [21] BINDING OF CC-1065 TO POLYNUCLEOTIDES AND OLIGONUCLEOTIDES
    KRUEGER, WC
    LI, LH
    MOSCOWITZ, A
    PRAIRIE, MD
    PETZOLD, G
    SWENSON, DH
    BIOPOLYMERS, 1985, 24 (08) : 1549 - 1572
  • [22] CC-1065 AND THE DUOCARMYCINS - UNRAVELING THE KEYS TO A NEW CLASS OF NATURALLY DERIVED DNA ALKYLATING-AGENTS
    BOGER, DL
    JOHNSON, DS
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (09) : 3642 - 3649
  • [23] ON THE MECHANISM OF INTERACTION OF CC-1065 WITH DNA
    SWENSON, DH
    KRUEGER, WC
    PETZOLD, GL
    WALLACE, TL
    LI, LH
    PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, 1982, 23 (MAR): : 196 - 196
  • [24] Fundamental Relationships between Structure, Reactivity, and Biological Activity for the Duocarmycins and CC-1065
    MacMillan, Karen S.
    Boger, Dale L.
    JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (19) : 5771 - 5780
  • [25] Synthesis and evaluation of duocarmycin and CC-1065 analogues containing modifications in the subunit linking amide
    J Org Chem, 14 (5241-5244):
  • [26] Synthesis and evaluation of duocarmycin and CC-1065 analogues containing modifications in the subunit linking amide
    Boger, DL
    Santillan, A
    Searcey, M
    Jin, Q
    JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (14): : 5241 - 5244
  • [27] Synthesis and evaluation of CC-1065 and duocarmycin analogs incorporating the iso-CBI alkylation subunit.
    Boger, DL
    Garbaccio, RM
    Jin, Q
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1997, 214 : 277 - ORGN
  • [28] INHIBITION OF T4 DNA-LIGASE ACTIVITY (+)-CC-1065 - DEMONSTRATION OF THE IMPORTANCE OF THE STIFFENING AND WINDING EFFECTS OF (+)-CC-1065 ON DNA
    SUN, DK
    HURLEY, LH
    ANTI-CANCER DRUG DESIGN, 1992, 7 (01): : 15 - 36
  • [29] DNA-BASE PAIR BINDING-SPECIFICITY OF CC-1065
    THERIAULT, NY
    KRUEGER, WC
    PRAIRIE, MD
    NUCLEOSIDES & NUCLEOTIDES, 1987, 6 (1-2): : 327 - 330
  • [30] THE COVALENT BINDING OF THE ANTI-TUMOR ANTIBIOTIC, CC-1065, TO DNA
    SWENSON, DH
    WOODLEY, BJ
    PETZOLD, GL
    SCAHILL, TA
    KAPLAN, DJ
    HURLEY, LH
    PROCEEDINGS OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, 1983, 24 (MAR): : 248 - 248
12345