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Stabilization of G-quadruplex DNA with platinum(II) Schiff base complexes: Luminescent probe and down-regulation of c-myc oncogene expression
Wu P.1; Ma D.-L.1; Leung C.-H.1; Yan S.-C.1; Zhu N.1; Abagyan R.2; Che C.-M.1
2009-12-07
Source PublicationChemistry - A European Journal
ISSN15213765 09476539
Volume15Issue:47Pages:13008-13021
AbstractThe interactions of a series of platinum(II) Schiff base complexes with c-myc G-quadruplex DNA were studied. Complex [PtL] (1a; H L= N,N'-bis(salicylidene)-4,5-methoxy-1,2- phenylenediamine) can moderately inhibit c-myc gene promoter activity in a cell-free system through stabilizing the G-quadruplex structure and can inhibit c-myc oncogene expression in cultured cells. The interaction between 1a and G-quadruplex DNA has been examined by H NMR spectroscopy. By using computer-aided structure-based drug design for hit-to-lead optimization, an in silico G-quadruplex DNA model has been constructed for docking-based virtual screening to develop new platinum(II) Schiff base complexes with improved inhibitory activities. Complex [PtL] (3; HL =N,N'-bis{4-[1-(2-propylpiperidine)oxy]salicylidene}-4,5-methoxy-1, 2-phenylenediamine) has been identified with a top score in the virtual screening. This complex was subsequently prepared and experimentally tested in vitro for its ability to stabilize or induce the formation of the c-myc G-quadruplex. The inhibitory activity of 3 (IC = 4.4 μm) is tenfold more than that of 1a. The interaction between 1a or 3 with c-myc G-quadruplex DNA has been examined by absorption titration, emission titration, molecular modeling, and NMR titration experiments, thus revealing that both 1a and 3 bind c-myc G-quadruplex DNA through an external end-stacking mode at the 3' terminal face of the G-quadruplex. Such binding of G-quadruplex DNA with 3 is accompanied by up to an eightfold increase in the intensity of photoluminescence at λ = 652 nm. Complex 3 also effectively down-regulated the expression of c-myc in human hepatocarcinoma cells. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
KeywordG-quadruplex DNA Luminescent probes Onogenes Platinum Schiff bases
DOI10.1002/chem.200901943
URLView the original
Language英語
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Cited Times [WOS]:115   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Institute of Molecular Technology for Drug Discovery and Synthesis, Hong Kong
2.University of California, San Diego
Recommended Citation
GB/T 7714
Wu P.,Ma D.-L.,Leung C.-H.,et al. Stabilization of G-quadruplex DNA with platinum(II) Schiff base complexes: Luminescent probe and down-regulation of c-myc oncogene expression[J]. Chemistry - A European Journal,2009,15(47):13008-13021.
APA Wu P..,Ma D.-L..,Leung C.-H..,Yan S.-C..,Zhu N..,...&Che C.-M..(2009).Stabilization of G-quadruplex DNA with platinum(II) Schiff base complexes: Luminescent probe and down-regulation of c-myc oncogene expression.Chemistry - A European Journal,15(47),13008-13021.
MLA Wu P.,et al."Stabilization of G-quadruplex DNA with platinum(II) Schiff base complexes: Luminescent probe and down-regulation of c-myc oncogene expression".Chemistry - A European Journal 15.47(2009):13008-13021.
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