Synthesis, DNA-/bovine serum albumin-binding affinity, and cytotoxicity of dinuclear platinum(II) complexes with 1,6-naphthyridine-bridging ligand.

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From: Applied Organometallic Chemistry(Vol. 35, Issue 3)
Publisher: Wiley Subscription Services, Inc.
Document Type: Report; Brief article
Length: 273 words

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Keywords: 1,6-naphthyridine; apoptosis; cytotoxicity; dinuclear platinum(II) complexes; DNA/BSA binding The dinuclear platinum(II) complexes, [{PtCl(NH.sub.3).sub.2}.sub.2([MU]-1,6-nphe)](ClO.sub.4).sub.2 (Pt1) and [{Pt(en)Cl}.sub.2([MU]-1,6-nphe)](ClO.sub.4).sub.2 (Pt2) (en is a bidentate-coordinated ethylenediamine and 1,6-nphe is the bridging 1,6-naphthyridine ligand) were synthesized and characterized by different spectroscopic methods. The DNA-binding evaluation of complexes Pt1 and Pt2 was done by UV-Vis, fluorescence emission spectroscopy, and their interaction with bovine serum albumin (BSA). The cytotoxic activity of these complexes was determined against mouse breast (4T1) and colon (CT26) cancer cell lines, human breast (MDA-MB-468), colon (HCT-116), and lung (A549) cancer cell lines as well as mouse mesenchymal stem cells (mMSC). Complex Pt1 showed higher cytotoxic capacity toward solid cancer cell lines compared with Pt2 and lower cytotoxic capacity toward mMSC cells compared with cisplatin. Furthermore, molecular mechanism studies showed that Pt1 complex induced 4T1 and A549 cell apoptosis therefore increasing expression of pro-apoptotic caspase-3 and decreasing expression of anti-apoptotic Bcl-2 and Ki-67. Antitumor capacity of Pt1 complex might be manifested at least in two ways: by facilitating apoptosis and by inhibiting tumor cells proliferation. CAPTION(S): Fig. S1 1H and 13C NMR spectrum of Pt1 and Pt2 (200 MHz (1H), 50 MHz (13C), D2O, 298 K). Figure S2 IR spectrum of Pt1 and Pt2 complexes (KBr pellet, 298 K) Figure S3. UV-Vis spectra of Pt1 and Pt2 complexes measured in 5·10-5 M water solution Figure S4. Dose-response curves for the treatment of 4T1, MDA-MB-468, CT26, HCT116, A549 and nonmalignant mMSC cells with Pt1, Pt2 and cisplatin determinate after 48 h incubation. Byline: Bata Konovalov, Andjela A. Franich, Marina Jovanovic, Milena Jurisevic, Nevena Gajovic, Marina Jovanovic, NebojÅ¡a Arsenijevic, Veljko Maric, Ivan Jovanovic, Marija D. Živkovic, Snežana Rajkovic

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Gale Document Number: GALE|A653645897