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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2010-5-6
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pubmed:abstractText |
The synthesis of a series of 24-membered pyridine-containing polyoxazole macrocycles is described. Seventeen new macrocycles were evaluated for cytotoxic activity against RPMI 8402, KB-3, and KB-3 cell lines that overexpress the efflux transporters MDR1 (KBV-1) and BCRP (KBH5.0). Macrocycles in which the pyridyl-polyoxazole moiety is linked by a 1,3-bis(aminomethyl)phenyl group with a 5-(2-aminoethyl)- (18) or a 5-(2-dimethylaminoethyl)- substituent (19) displayed the greatest cytotoxic potency. These compounds exhibit exquisite selectivity for stabilizing G-quadruplex DNA with no stabilization of duplex DNA or RNA. Compound 19 stabilizes quadruplex mRNA that encodes the cell-cycle checkpoint protein kinase Aurora A to a greater extent than the quadruplex DNA of a human telomeric sequence. These data may suggest a role for G-quadruplex ligands interacting with mRNA being associated with the biological activity of macrocyclic polyoxazoles. Compound 19 has significant in vivo anticancer activity against a human breast cancer xenograft (MDA-MB-435) in athymic nude mice.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-10498189,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-10739869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-10740289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-10804580,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-11222758,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-11456694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-11745111,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-11878947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-12369989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-12467228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-14679002,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-16253503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-16302000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-16652154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-16735121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-1680024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-16866556,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-17217265,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-17452355,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-17915931,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-18248989,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-18439430,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-18515097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-18776218,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-19531483,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-19911822,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-3039492,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-5118648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-9216827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-949539,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20359224-9730808
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABCB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ABCG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Macrocyclic Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazoles,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
13
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3632-44
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pubmed:dateRevised |
2011-7-28
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pubmed:meshHeading |
pubmed-meshheading:20359224-ATP-Binding Cassette Transporters,
pubmed-meshheading:20359224-Animals,
pubmed-meshheading:20359224-Antineoplastic Agents,
pubmed-meshheading:20359224-Breast Neoplasms,
pubmed-meshheading:20359224-Carrier Proteins,
pubmed-meshheading:20359224-Cell Line, Tumor,
pubmed-meshheading:20359224-DNA,
pubmed-meshheading:20359224-Drug Screening Assays, Antitumor,
pubmed-meshheading:20359224-G-Quadruplexes,
pubmed-meshheading:20359224-Humans,
pubmed-meshheading:20359224-Ligands,
pubmed-meshheading:20359224-Macrocyclic Compounds,
pubmed-meshheading:20359224-Mice,
pubmed-meshheading:20359224-Mice, Nude,
pubmed-meshheading:20359224-Neoplasm Proteins,
pubmed-meshheading:20359224-Oxazoles,
pubmed-meshheading:20359224-P-Glycoprotein,
pubmed-meshheading:20359224-Pyridines,
pubmed-meshheading:20359224-RNA,
pubmed-meshheading:20359224-Xenograft Model Antitumor Assays
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pubmed:year |
2010
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pubmed:articleTitle |
Macrocyclic pyridyl polyoxazoles: selective RNA and DNA G-quadruplex ligands as antitumor agents.
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pubmed:affiliation |
Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854-8020, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.
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