File Download
  • No File Attached
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Antitumor agents 294. Novel E-ring-modified camptothecin-4β-anilino- 4′-O-demethyl-epipodophyllotoxin conjugates as DNA topoisomerase i inhibitors and cytotoxic agents
  • Basic View
  • Metadata View
  • XML View
TitleAntitumor agents 294. Novel E-ring-modified camptothecin-4β-anilino- 4′-O-demethyl-epipodophyllotoxin conjugates as DNA topoisomerase i inhibitors and cytotoxic agents
 
AuthorsYe, D4
Shi, Q4
Leung, CH2
Kim, SW2
Park, SY2
Gullen, EA2
Jiang, ZL2
Zhu, H1
MorrisNatschke, SL4
Cheng, YC2
Lee, KH4 3
 
KeywordsCamptothecin (Cpt)
Conjugates
Cytotoxicity
Epipodophyllotoxin
Etoposide (Vp-16)
Topoisomerase
 
Issue Date2012
 
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/bmc
 
CitationBioorganic And Medicinal Chemistry, 2012, v. 20 n. 14, p. 4489-4494 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.bmc.2012.05.030
 
AbstractTwo conjugates (1 and 2) of camptothecin (CPT) and 4β-anilino- 4′-O-demethylepipodophyllotoxin were previously shown to exert antitumor activity through inhibition of topoisomerase I (topo I). In this current study, two novel conjugates (1E and 2E) with an open E-ring in the CPT moiety were first synthesized and evaluated for biological activity in comparison with their intact E-ring congeners. This novel class of CPT-derivatives exhibits its antitumor effect against CPT-sensitive and -resistant cells, in part, by inhibiting topo I-linked DNA (TLD) religation. An intact E-ring was not essential for the inhibition of TLD religation, although conjugates with an open E-ring were less potent than the closed ring analogs. This lower religation potency resulted in decreased formation of protein-linked DNA breaks (PLDBs), and hence, less cell growth inhibition. In addition to their impact on topo I, conjugates 1E, 2, and 2E exhibited a minor inhibitory effect on topo II-induced DNA cleavage. The novel structures of 1E and 2E may present scaffolds for further development of dual function topo I and II inhibitors with improved pharmacological profiles and physicochemical properties. © 2012 Elsevier Ltd. All rights reserved.
 
ISSN0968-0896
2013 Impact Factor: 2.951
 
DOIhttp://dx.doi.org/10.1016/j.bmc.2012.05.030
 
ISI Accession Number IDWOS:000305952500036
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorYe, D
 
dc.contributor.authorShi, Q
 
dc.contributor.authorLeung, CH
 
dc.contributor.authorKim, SW
 
dc.contributor.authorPark, SY
 
dc.contributor.authorGullen, EA
 
dc.contributor.authorJiang, ZL
 
dc.contributor.authorZhu, H
 
dc.contributor.authorMorrisNatschke, SL
 
dc.contributor.authorCheng, YC
 
dc.contributor.authorLee, KH
 
dc.date.accessioned2012-10-08T03:23:56Z
 
dc.date.available2012-10-08T03:23:56Z
 
dc.date.issued2012
 
dc.description.abstractTwo conjugates (1 and 2) of camptothecin (CPT) and 4β-anilino- 4′-O-demethylepipodophyllotoxin were previously shown to exert antitumor activity through inhibition of topoisomerase I (topo I). In this current study, two novel conjugates (1E and 2E) with an open E-ring in the CPT moiety were first synthesized and evaluated for biological activity in comparison with their intact E-ring congeners. This novel class of CPT-derivatives exhibits its antitumor effect against CPT-sensitive and -resistant cells, in part, by inhibiting topo I-linked DNA (TLD) religation. An intact E-ring was not essential for the inhibition of TLD religation, although conjugates with an open E-ring were less potent than the closed ring analogs. This lower religation potency resulted in decreased formation of protein-linked DNA breaks (PLDBs), and hence, less cell growth inhibition. In addition to their impact on topo I, conjugates 1E, 2, and 2E exhibited a minor inhibitory effect on topo II-induced DNA cleavage. The novel structures of 1E and 2E may present scaffolds for further development of dual function topo I and II inhibitors with improved pharmacological profiles and physicochemical properties. © 2012 Elsevier Ltd. All rights reserved.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationBioorganic And Medicinal Chemistry, 2012, v. 20 n. 14, p. 4489-4494 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.bmc.2012.05.030
 
dc.identifier.citeulike10698222
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.bmc.2012.05.030
 
dc.identifier.epage4494
 
dc.identifier.isiWOS:000305952500036
 
dc.identifier.issn0968-0896
2013 Impact Factor: 2.951
 
dc.identifier.issue14
 
dc.identifier.pmid22698783
 
dc.identifier.scopuseid_2-s2.0-84863212686
 
dc.identifier.spage4489
 
dc.identifier.urihttp://hdl.handle.net/10722/168646
 
dc.identifier.volume20
 
dc.languageeng
 
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/bmc
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofBioorganic and Medicinal Chemistry
 
dc.relation.referencesReferences in Scopus
 
dc.subjectCamptothecin (Cpt)
 
dc.subjectConjugates
 
dc.subjectCytotoxicity
 
dc.subjectEpipodophyllotoxin
 
dc.subjectEtoposide (Vp-16)
 
dc.subjectTopoisomerase
 
dc.titleAntitumor agents 294. Novel E-ring-modified camptothecin-4β-anilino- 4′-O-demethyl-epipodophyllotoxin conjugates as DNA topoisomerase i inhibitors and cytotoxic agents
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Ye, D</contributor.author>
<contributor.author>Shi, Q</contributor.author>
<contributor.author>Leung, CH</contributor.author>
<contributor.author>Kim, SW</contributor.author>
<contributor.author>Park, SY</contributor.author>
<contributor.author>Gullen, EA</contributor.author>
<contributor.author>Jiang, ZL</contributor.author>
<contributor.author>Zhu, H</contributor.author>
<contributor.author>MorrisNatschke, SL</contributor.author>
<contributor.author>Cheng, YC</contributor.author>
<contributor.author>Lee, KH</contributor.author>
<date.accessioned>2012-10-08T03:23:56Z</date.accessioned>
<date.available>2012-10-08T03:23:56Z</date.available>
<date.issued>2012</date.issued>
<identifier.citation>Bioorganic And Medicinal Chemistry, 2012, v. 20 n. 14, p. 4489-4494</identifier.citation>
<identifier.issn>0968-0896</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/168646</identifier.uri>
<description.abstract>Two conjugates (1 and 2) of camptothecin (CPT) and 4&#946;-anilino- 4&#8242;-O-demethylepipodophyllotoxin were previously shown to exert antitumor activity through inhibition of topoisomerase I (topo I). In this current study, two novel conjugates (1E and 2E) with an open E-ring in the CPT moiety were first synthesized and evaluated for biological activity in comparison with their intact E-ring congeners. This novel class of CPT-derivatives exhibits its antitumor effect against CPT-sensitive and -resistant cells, in part, by inhibiting topo I-linked DNA (TLD) religation. An intact E-ring was not essential for the inhibition of TLD religation, although conjugates with an open E-ring were less potent than the closed ring analogs. This lower religation potency resulted in decreased formation of protein-linked DNA breaks (PLDBs), and hence, less cell growth inhibition. In addition to their impact on topo I, conjugates 1E, 2, and 2E exhibited a minor inhibitory effect on topo II-induced DNA cleavage. The novel structures of 1E and 2E may present scaffolds for further development of dual function topo I and II inhibitors with improved pharmacological profiles and physicochemical properties. &#169; 2012 Elsevier Ltd. All rights reserved.</description.abstract>
<language>eng</language>
<publisher>Pergamon. The Journal&apos;s web site is located at http://www.elsevier.com/locate/bmc</publisher>
<relation.ispartof>Bioorganic and Medicinal Chemistry</relation.ispartof>
<subject>Camptothecin (Cpt)</subject>
<subject>Conjugates</subject>
<subject>Cytotoxicity</subject>
<subject>Epipodophyllotoxin</subject>
<subject>Etoposide (Vp-16)</subject>
<subject>Topoisomerase</subject>
<title>Antitumor agents 294. Novel E-ring-modified camptothecin-4&#946;-anilino- 4&#8242;-O-demethyl-epipodophyllotoxin conjugates as DNA topoisomerase i inhibitors and cytotoxic agents</title>
<type>Article</type>
<description.nature>link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1016/j.bmc.2012.05.030</identifier.doi>
<identifier.pmid>22698783</identifier.pmid>
<identifier.scopus>eid_2-s2.0-84863212686</identifier.scopus>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-84863212686&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>20</identifier.volume>
<identifier.issue>14</identifier.issue>
<identifier.spage>4489</identifier.spage>
<identifier.epage>4494</identifier.epage>
<identifier.isi>WOS:000305952500036</identifier.isi>
<publisher.place>United Kingdom</publisher.place>
<identifier.citeulike>10698222</identifier.citeulike>
</item>
Author Affiliations
  1. Rutgers University-Camden campus
  2. Yale University
  3. China Medical University Hospital Taichung
  4. The University of North Carolina at Chapel Hill