Source:http://linkedlifedata.com/resource/pubmed/id/10464026
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
17
|
pubmed:dateCreated |
1999-9-20
|
pubmed:abstractText |
A series of 5-amino-seco-CBI compounds, designed for use as effectors for prodrugs, were prepared to study structure-activity relationships for the cytotoxicity of side chain analogues. Compounds were prepared by coupling 1-(chloromethyl)-5-nitro-1, 2-dihydro-3H-benz[e]indole to appropriate carboxylic acids, followed by nitro group reduction, or by coupling suitable 5-amino-protected indolines to alpha,beta-unsaturated acids, followed by deblocking. These AT-specific DNA alkylating agents were evaluated for cytotoxicity in a series of tumor cell lines (AA8, UV4, EMT6, SKOV3). For those analogues bearing an indolecarbonyl side chain, the 5'-methoxy derivative was the most cytotoxic (IC(50) 1.3 nM in AA8 cells, 4 h exposure), comparable to that of the parent CBI-TMI (5', 6',7'-trimethoxyindole) derivative (IC(50) 0.46 nM in the above assay). A subset of solubilized derivatives bearing O(CH(2))(2)NMe(2) substituents were about 10-fold less potent. For compounds containing an acryloyl linker in the side chain, the 4'-methoxycinnamoyl derivative proved the most cytotoxic (IC(50) 0. 09 nM in the above assay). A number of these 5-amino-seco-CBI-TMI analogues (including the solubilized compounds) are of interest both as cytotoxins and as components of amine-based prodrugs designed for tumor-specific activation.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Aug
|
pubmed:issn |
0022-2623
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
26
|
pubmed:volume |
42
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
3400-11
|
pubmed:dateRevised |
2007-11-14
|
pubmed:meshHeading |
pubmed-meshheading:10464026-Animals,
pubmed-meshheading:10464026-Antineoplastic Agents, Alkylating,
pubmed-meshheading:10464026-DNA,
pubmed-meshheading:10464026-Drug Screening Assays, Antitumor,
pubmed-meshheading:10464026-Indoles,
pubmed-meshheading:10464026-Inhibitory Concentration 50,
pubmed-meshheading:10464026-Male,
pubmed-meshheading:10464026-Mice,
pubmed-meshheading:10464026-Mice, Inbred C3H,
pubmed-meshheading:10464026-Stereoisomerism,
pubmed-meshheading:10464026-Structure-Activity Relationship,
pubmed-meshheading:10464026-Tumor Cells, Cultured
|
pubmed:year |
1999
|
pubmed:articleTitle |
5-Amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles: relationships between structure and cytotoxicity for analogues bearing different DNA minor groove binding subunits.
|
pubmed:affiliation |
Auckland Cancer Society Research Centre, Faculty of Medicine and Health Science, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|