Linked Life Data

10363025

Source:http://linkedlifedata.com/resource/pubmed/id/10363025

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-6-25
pubmed:abstractText
Certain DNA minor groove binding agents, distamycin, netropsin, and a series of anticancer bis-benzimidazoles can block DNA helicase activity by binding to duplex DNA at specific base sequences. DNA helicases are crucial to cell DNA replication, transcription and repair because these enzymes separate double-stranded DNA, thereby preparing the strands for enzymatic manipulation. From our studies we have developed a hypothesis that focuses on cellular DNA helicase action as a mechanistic site where these minor groove binders can act. A crucial aspect for modulation of DNA activity by drugs is for specificity and selectivity. A series of DNA-interactive bis-benzimidazole analogues of Hoechst 33258 was also prepared to explore the potential for anticancer activity mediated for certain of the drugs via bioreductive activation by endogenous NADH or NADPH. The biological endpoints examined included intracellular distribution in euoxic and hypoxic conditions observed by fluorescence microscopy; relative efficacy as antimetabolites determined by the MTT [tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay in euoxic and hypoxic conditions; and relative inhibitory activities on human DNA helicase, as determined by degree of dissociation of GC B6486 DNA. The intracellular distribution was unique to each of the test compounds. Compounds V-93 and V-153, the respective semiquinone and quinone derivatives, demonstrated the predicted enhanced cytotoxicity and anti-helicase activities, supporting the concept that preferential binding of DNA at 5'-CG and TG sequences provides a novel approach to anticancer drug development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0266-9536
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19-36
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Bis-benzimidazole anticancer agents: targeting human tumour helicases.
pubmed:affiliation
Noujaim Institute for Pharmaceutical Oncology Research, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, Alberta, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't