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Article: Organoplatinum(II) complexes with nucleobase motifs as inhibitors of human topoisomerase II catalytic activity

TitleOrganoplatinum(II) complexes with nucleobase motifs as inhibitors of human topoisomerase II catalytic activity
Authors
KeywordsCancer
DNA
Inhibitors
Nucleobases
Platinum
Issue Date2010
PublisherWiley - V C H Verlag GmbH & Co. KGaA. The Journal's web site is located at http://www.wiley-vch.de/publish/en/journals/alphabeticIndex/2451
Citation
Chemistry - An Asian Journal, 2010, v. 5 n. 10, p. 2271-2280 How to Cite?
AbstractPlatinum(II) complexes bearing acetylide ligands containing nucleobase motifs are prepared and their impact on human topoisomerase II (TopoII) is evaluated. Both platinum( II) complexes [Pt II(C∧N∧N)- (C≡CCH 2R)] (1a-c) and [Pt II(tBu 3terpy) (C≡CCH 2R)]+ (2a-c) (C∧N∧N=6-phenyl-2,2′- bipyridyl, tBu 3terpy=4,4′,4″-tri-tert-butyl-2,2′: 6′,2″-terpyridyl, and R=(a) adenine, (b) thymine, and (c) 2-amino-6-chloropurine) are stable in aqueous solutions for 48 hours at room temperature. The binding constants (K) for the platinum(II) complexes towards calf thymus DNA are in the order of 10 5 dm 3mol -1 as estimated by using UV/Vis absorption spectroscopy. Of the complexes examined, only complexes 1a-c are found to behave as intercalators. Both complexes 1a-c and 2a-c inhibit TopoII-induced relaxation of supercoiled DNA, while 2c is the most potent TopoII inhibitors among the tested compounds. Inhibition of DNA relaxation is detected at nanomolar concentrations of 2c. All of the platinum(II) complexes are cytotoxic to human cancer cells with IC 50 values of 0.5-13.7 μm, while they are less toxic against normal cells CCD-19 Lu. © 2010 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.
Persistent Identifierhttp://hdl.handle.net/10722/134355
ISSN
2015 Impact Factor: 4.592
2015 SCImago Journal Rankings: 1.833
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong Hong Kong, Research Grant Council (HKU)HKU 7052/07P
University Grants Committee of the Hong Kong Special Administrative Region, ChinaAoE/P-10/01
Innovation Technology FundITS/134/09FP
Funding Information:

We are thankful for the financial support of The University of Hong Kong (University Development Fund), Hong Kong Research Grant Council (HKU 7052/07P), and the Areas of Excellence Scheme established under the University Grants Committee of the Hong Kong Special Administrative Region, China (AoE/P-10/01), and Innovation Technology Fund (ITS/134/09FP) administered by Innovation Technology Commission of Hong Kong Special Administrative Region, China.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorWang, Pen_HK
dc.contributor.authorLeung, CHen_HK
dc.contributor.authorMa, DLen_HK
dc.contributor.authorLu, Wen_HK
dc.contributor.authorChe, CMen_HK
dc.date.accessioned2011-06-17T09:18:31Z-
dc.date.available2011-06-17T09:18:31Z-
dc.date.issued2010en_HK
dc.identifier.citationChemistry - An Asian Journal, 2010, v. 5 n. 10, p. 2271-2280en_HK
dc.identifier.issn1861-4728en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134355-
dc.description.abstractPlatinum(II) complexes bearing acetylide ligands containing nucleobase motifs are prepared and their impact on human topoisomerase II (TopoII) is evaluated. Both platinum( II) complexes [Pt II(C∧N∧N)- (C≡CCH 2R)] (1a-c) and [Pt II(tBu 3terpy) (C≡CCH 2R)]+ (2a-c) (C∧N∧N=6-phenyl-2,2′- bipyridyl, tBu 3terpy=4,4′,4″-tri-tert-butyl-2,2′: 6′,2″-terpyridyl, and R=(a) adenine, (b) thymine, and (c) 2-amino-6-chloropurine) are stable in aqueous solutions for 48 hours at room temperature. The binding constants (K) for the platinum(II) complexes towards calf thymus DNA are in the order of 10 5 dm 3mol -1 as estimated by using UV/Vis absorption spectroscopy. Of the complexes examined, only complexes 1a-c are found to behave as intercalators. Both complexes 1a-c and 2a-c inhibit TopoII-induced relaxation of supercoiled DNA, while 2c is the most potent TopoII inhibitors among the tested compounds. Inhibition of DNA relaxation is detected at nanomolar concentrations of 2c. All of the platinum(II) complexes are cytotoxic to human cancer cells with IC 50 values of 0.5-13.7 μm, while they are less toxic against normal cells CCD-19 Lu. © 2010 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.en_HK
dc.languageengen_US
dc.publisherWiley - V C H Verlag GmbH & Co. KGaA. The Journal's web site is located at http://www.wiley-vch.de/publish/en/journals/alphabeticIndex/2451en_HK
dc.relation.ispartofChemistry - An Asian Journalen_HK
dc.subjectCanceren_HK
dc.subjectDNAen_HK
dc.subjectInhibitorsen_HK
dc.subjectNucleobasesen_HK
dc.subjectPlatinumen_HK
dc.titleOrganoplatinum(II) complexes with nucleobase motifs as inhibitors of human topoisomerase II catalytic activityen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1861-4728&volume=5&issue=10&spage=2271&epage=2280&date=2010&atitle=Organoplatinum(II)+complexes+with+nucleobase+motifs+as+inhibitors+of+human+topoisomerase+II+catalytic+activity-
dc.identifier.emailLeung, CH:duncanl@hkucc.hku.hken_HK
dc.identifier.emailMa, DL:edmondma@hku.hken_HK
dc.identifier.emailLu, W:luwei@hku.hken_HK
dc.identifier.emailChe, CM:cmche@hku.hken_HK
dc.identifier.authorityLeung, CH=rp00730en_HK
dc.identifier.authorityMa, DL=rp00760en_HK
dc.identifier.authorityLu, W=rp00754en_HK
dc.identifier.authorityChe, CM=rp00670en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/asia.201000451en_HK
dc.identifier.pmid20730852-
dc.identifier.scopuseid_2-s2.0-77957587101en_HK
dc.identifier.hkuros185606en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77957587101&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume5en_HK
dc.identifier.issue10en_HK
dc.identifier.spage2271en_HK
dc.identifier.epage2280en_HK
dc.identifier.isiWOS:000283272000018-
dc.publisher.placeGermanyen_HK
dc.relation.projectDiscovery and Pre-Clinical Evaluation of Promising Metal-Based Anti-Cancer Drug Leads-
dc.relation.projectInstitute of molecular technology for drug discovery and synthesis-
dc.identifier.scopusauthoridWang, P=36571041500en_HK
dc.identifier.scopusauthoridLeung, CH=7402612570en_HK
dc.identifier.scopusauthoridMa, DL=7402075538en_HK
dc.identifier.scopusauthoridLu, W=27868087600en_HK
dc.identifier.scopusauthoridChe, CM=7102442791en_HK

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