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2015

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/164842

Neutral and ionic platinum compounds containing a cyclometalated chiral primary amine: Synthesis, antitumor activity, DNA interaction and topoisomerase I - cathepsin B inhibition

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https://doi.org/10.1039/c5dt01713k

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The synthesis and preliminary biological evaluation of neutral and cationic platinum derivatives of chiral 1-(1-naphthyl)ethylamine are reported, namely cycloplatinated neutral complexes [PtCl{(R or S)-NH(2)CH(CH(3))C(10)H(6)}(L)] [L = SOMe(2) ( 1-R or 1-S ), L = PPh(3) (2-R or 2-S), L = P(4-FC(6)H(4))(3) (3-R), L = P(CH(2))(3)N(3)(CH(2))(3) (4-R)], cycloplatinated cationic complexes [Pt{(R)-NH(2)CH(CH(3))C(10)H(6)}{L}]Cl [L = Ph(2)PCH(2)CH(2)PPh(2) (5-R), L = (C(6)F(5))(2)PCH(2)CH(2)P(C(6)F(5))(2) (6-R)] and the Pt(ii) coordination compound trans-[PtCl(2){(R)-NH(2)CH(CH(3))C(10)H(6)}(2)] (7-R). The X-ray molecular structure of 7-R is reported. The cytotoxic activity against a panel of human adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116 colon), cell cycle arrest and apoptosis, DNA interaction, topoisomerase I and cathepsin B inhibition, and Pt cell uptake of the studied compounds are presented. Remarkable cytotoxicity was observed for most of the synthesized Pt(ii) compounds regardless of (i) the absolute configuration R or S, and (ii) the coordinated/cyclometallated (neutral or cationic) nature of the complexes. The most potent compound 2-R (IC(50) = 270 nM) showed a 148-fold increase in potency with regard to cisplatin in HCT-116 colon cancer cells. Preliminary biological results point out to different biomolecular targets for the investigated compounds. Neutral cyclometallated complexes 1-R and 2-R, modify the DNA migration as cisplatin, cationic platinacycle 5-R was able to inhibit topoisomerase I-promoted DNA supercoiling, and Pt(ii) coordination compound 7-R turned out to be the most potent inhibitor of cathepsin B. Induction of G-1 phase ( 2-R and 5-R ), and S and G-2 phases (6-R) arrests are related to the antiproliferative activity of some representative compounds upon A-549 cells. Induction of apoptosis is also observed for 2-R and 6-R.

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Platí, Càncer

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Platinum, Cancer

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Articles publicats en revistes (Mineralogia, Petrologia i Geologia Aplicada)

Citació

ALBERT MACH, Joan, BOSQUE PUEYO, Ramón, CRESPO, M., GRANELL SANVICENTE, Jaime ramón, LÓPEZ MARTÍNEZ, Ma. concepción, MARTÍN, Raquel, GONZÁLEZ, A., JAYARAMAN, A., QUIRANTE SERRANO, Josefina, CALVIS, Carme, BADÍA PALACÍN, Josefa, BALDOMÀ LLAVINÉS, Laura, FONT BARDIA, Ma. mercedes, CASCANTE I SERRATOSA, Marta, MESSEGUER I PEYPOCH, Ramon. Neutral and ionic platinum compounds containing a cyclometalated chiral primary amine: Synthesis, antitumor activity, DNA interaction and topoisomerase I - cathepsin B inhibition. _Dalton Transactions_. 2015. Vol. 44, núm. 30, pàgs. 13602-13614. [consulta: 14 de gener de 2026]. ISSN: 1477-9226. [Disponible a: https://hdl.handle.net/2445/164842]

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