Linked Life Data

10821671

Source:http://linkedlifedata.com/resource/pubmed/id/10821671

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2000-6-21
pubmed:abstractText
We found that a group of rubromycins and their analogues, a class of quinone antibiotics that possesses benzofuran and benzodipyran rings to form a spiroketal system, strongly inhibited human telomerase as assessed with a modified telomeric repeat amplification protocol. beta- and gamma-Rubromycins and purpuromycin appeared to be the most potent telomerase inhibitors, with 50% inhibitory concentrations (IC(50)) of about 3 microM, and griseorhodins A and C also showed comparable potencies for the inhibition (IC(50) = 6-12 microM). In contrast, opening of the spiroketal system of beta-rubromycin, giving rise to alpha-rubromycin, substantially decreased its inhibitory potency toward telomerase (IC(50) > 200 microM), indicating the essential role of the spiroketal system in telomerase inhibition. A kinetic study of the inhibition by beta-rubromycin revealed a competitive interaction with respect to the telomerase substrate primer, with a K(i) of 0.74 microM, whereas a mixed type inhibition was observed with respect to the nucleotide substrate. beta-Rubromycin was also potent in inhibiting retroviral reverse transcriptases but had virtually no effect on other DNA/RNA-modifying enzymes including DNA and RNA polymerases, deoxyribonuclease, and topoisomerase. Although beta-rubromycin showed nonspecific cytotoxicities, reducing proliferation of cancer cells (IC(50) approximately 20 microM), we conclude that beta-rubromycin appears to be a lead structure for the development of more potent and selective inhibitors of human telomerase.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Growth Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Naphthoquinones, http://linkedlifedata.com/resource/pubmed/chemical/Quinones, http://linkedlifedata.com/resource/pubmed/chemical/Reverse Transcriptase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Spiro Compounds, http://linkedlifedata.com/resource/pubmed/chemical/Telomerase, http://linkedlifedata.com/resource/pubmed/chemical/alpha-rubromycin, http://linkedlifedata.com/resource/pubmed/chemical/beta-rubromycin, http://linkedlifedata.com/resource/pubmed/chemical/gamma-rubromycin, http://linkedlifedata.com/resource/pubmed/chemical/griseorhodins, http://linkedlifedata.com/resource/pubmed/chemical/purpuromycin
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5995-6002
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Inhibition of human telomerase by rubromycins: implication of spiroketal system of the compounds as an active moiety.
pubmed:affiliation
Pharmaceuticals & Biotechnology Laboratory, Japan Energy Corporation, Toda-shi, Saitama, 335-8502 Japan.
pubmed:publicationType
Journal Article